Criteria for Inclusion of Subjects: Hand and forearm amputees: 1. Male or female, age 18 and older, of any race or ethnicity 2. Able and willing to sign Consent 3. Able and willing to participate in all study activities including implantation, testing and explantation of the study device. 4. Able to communicate effectively in English without an interpreter After preliminary screening subjects will be assessed for the following inclusion criteria: 1. Patient has an existing myoelectric hand prosthesis and demonstrates proficiency during daily use 2. Overall and phantom pain are well-controlled and not incapacitating Criteria for Exclusion of Subjects: 1. If MR neurogram and EMG/NCS study show nerve or muscle dysfunction/injury at a higher level than anticipated based on the appearance of the physical amputation stump, the subject may be excluded from the study due to adverse neuromuscular anatomy which would preclude use of the proposed experimental electrode implants. The radiographs will be used to confirm suitability of the amputation stump configuration. If the bony anatomy of the amputation stump is found to be unsuitable, the patient may be excluded from the study. 2. Subjects who have a history of cardiac arrhythmia will be excluded from the study.

• Histologically or cytologically-confirmed Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, or osteosarcoma
• Disease progression after prior therapy in locally advanced or metastatic setting
• Measurable or evaluable disease based on the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria
• Age 12 months to <21 years
• Adequate bone marrow reserves, hepatic function, and renal function
• Recovered from effects of any prior surgery or cancer therapy
• Patients 18 years or older will provide written consent. A parent or legal guardian of a patient <18 years of age will provide informed consent and patients 11 to 18 years of age will provide written assent or as per participating institutional policy.
• Clinically significant gastrointestinal disorders
• NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure
• Active infection or unexplained fever
• Known hypersensitivity to any of the components of MM-398 or other liposomal products
• Recent Investigational therapy
• Pregnant or breast feeding; females of child-bearing potential must test negative for pregnancy at the time of enrollment

• Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping
• Stable dose of oral corticosteroids for at least 24 weeks
• Intact right and left biceps or 2 alternative upper muscle groups
• Mean 6MWT greater than or equal 300 meters and less than or equal to 450 meters
• Stable pulmonary function: forced vital capacity (FVC) equal to or greater than 50% predicted
• Treatment with gene therapy at any time
• Previous treatment with SMT C1100, PRO045 (BMN 045), PRO053 (BMN 053) or PRO051 (BMN 051) within 24 weeks prior to Week 1
• Current or previous treatment with any other experimental treatment (other than deflazacort) within 12 weeks prior to Week 1
• Major surgery within 3 months prior to Week 1
• Presence of other clinically significant illness Other inclusion/exclusion criteria may apply

1. Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on Revised INRC criteria at the time of study enrollment with recurrent or progressive disease at any time prior to enrollment, regardless of overall response to frontline therapy, where frontline therapy includes a minimum of 4 cycles of induction therapy at any time prior to enrollment. 2. May have had prior 131I-MIBG therapy, provided: 1. It has been at least 6 months from the date of last 131I-MIBG ; 2. Response was other than progressive disease on first restaging after 131I-MIBG ; 3. Prior 131I-MIBG was given as monotherapy and not in combination with systemic anticancer agents; 4. Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg. 3. All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on an (123I)-iobenguane scan, or 1. any progressive non-iobenguane avid lesion is proven by biopsy to be a non-neuroblastoma lesion. 2. any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by routine imaging and confirmed by the investigator. 4. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least 2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment). 5. If a male, must agree to use an adequate contraception method as deemed appropriate by the Investigator (e.g., vasectomy, condoms) or partner using effective contraception and to not donate sperm during the study and for 90 days after receiving the last dose of study drug. 6. If a female of childbearing potential, have a negative serum pregnancy test result prior to each dosing and, if sexually active, be practicing an effective method of birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout the study. 7. Age at study entry ≥1 year. 8. Previous platelet transfusions are permitted, as long as the subject has a platelet count ≥50,000/μL without transfusion support for at least 1 week. 9. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline. 10. An absolute neutrophil count ≥750/μL without growth factor for 5 days. 11. Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age, and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartate aminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit of normal (for all sites, the upper limit of normal for alanine aminotransferase is defined as 45 U/L). 12. Normal thyroid function as measured by T4 or TSH or have abnormal results that are not considered clinically important by the Investigator or may be receiving levothyroxine. 13. Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior to Visit 1 (Baseline). 14. Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance Status Performance Status (for subjects 1 to 16 years of age) ≥50%. 15. Full recovery from the toxic effects of any prior therapy. 16. Coagulation Function: 1. International Normalized Ratio (INR) < 1.5 2. Partial thromboplastin time (PTT) < 1.5 times upper limit of normal. 1. Subjects within 5 half-lives after any antibody-based immunotherapy, or have not recovered from effects of any biologic therapy. 2. Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant. 3. Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit 1 are excluded. Those who have received allogeneic stem cell treatment more than 4 months from Visit 1 must have recovered and have no active graft versus host disease (GVHD) to be eligible. 4. Subjects must not have received radiation for a minimum of 2 weeks prior to study enrollment. Subjects whose only site(s) of disease have been radiated are eligible as long as the subject has MIBG avidity 2 weeks after completion of radiation. A minimum of 12 weeks prior to study enrollment is required following prior large field radiation therapy (ie, craniospinal, whole abdominal, total lung, > 50% marrow space) 5. History of total body irradiation. 6. Subjects do not have adequate renal function defined as GFR ≥ 70 mL/min/1.73 m2 either by creatinine clearance or radioisotope direct measurement or by calculation with the Schwartz formula 7. Subjects who are on hemodialysis. 8. Pregnancy or breastfeeding. 9. Significant active infections including active hepatitis B, or hepatitis C infection, or known infection with human immunodeficiency virus (HIV) (testing for HIV is not required prior to study entry). 10. Clinically important cardiac, pulmonary, and hepatic impairment. 11. Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy) 1. Since valproic acid has HDAC inhibitory activity, patients must not have received valproic acid within 30 days of study entry. 2. Since vorinostat may prolong the QT interval, patients must not be receiving other medications known to prolong the QT interval at the time of study entry . Pentamidine must not have been received within 1 week of study enrollment. 3. Patients with a history of deep venous thrombosis that was not associated with the presence of a central venous catheter. 4. Patients who are receiving Coumadin.

Key Inclusion Criteria
• Patients ≥6 months and up to 60 months (1800 days) of age at time of dosing following diagnostic confirmation during screening period by genotype who demonstrate the ability to sit unassisted for 10 or more seconds but cannot stand or walk
• Diagnostic confirmation by genotype includes lab documentation of homozygous absence of SMN1 exon 7; with exactly three copies of SMN2
• Negative gene testing for SMN2 gene modifier mutation (c.859G>C)
• Onset of clinical signs and symptoms consistent with spinal muscular atrophy (SMA) at < 12 months of age
• Able to sit independently and not standing or walking independently. Definition of sitting independently is defined by the World Health Organization Multicentre Growth Reference Study (WHO-MGRS) criteria of being able to sit up unsupported with head erect for at least 10 seconds. Child should not use arms or hands to balance body or support position (Wijnhoven 2004)
• Be up-to-date on childhood vaccines that include palivizumab prophylaxis (also known as Synagis) to prevent respiratory syncytial virus (RSV) infections are also recommended in accordance with American Academy of Pediatrics (AAP 2009) Key Exclusion Criteria
• Current or historical ability to stand or walk independently
• Contraindications for spinal tap procedure or administration of intrathecal therapy or presence of an implanted shunt for the drainage of CSF or an implanted central venous (CNS) catheter
• Severe contractures as determined by designated Physical Therapist(s) at screening that interfere with either the ability to attain/demonstrate functional measures or interferes with ability to receive intrathecal (IT) dosing
• Severe scoliosis (defined as ≥ 50° curvature of spine) evident on X-ray examination
• Previous, planned or expected scoliosis repair surgery/procedure within 1 year of dose administration
• Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry < 95% saturation at screening while the patient is awake, or for high altitudes > 1000 m, oxygen saturation < 92% while the patient is awake
• Pulse oximetry saturation must not decrease ≥ four (4) percentage points between screening and highest value on day of dosing
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods (i.e., nasogastric tube or nasojejunal tube) or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion
• Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two (2) weeks prior to dosing
• Medical necessity for a gastric feeding tube, where the majority of feedings are given by non-oral methods or patients whose weight-for-age falls below the 3rd percentile based on WHO Child Growth Standards (Onis 2006). Placement of a permanent gastrostomy prior to screening is not an exclusion
• Active viral infection (includes human immunodeficiency virus (HIV) or serology positive for hepatitis B or C, or Zika virus)
• Serious non-respiratory tract illness requiring systemic treatment and/or hospitalization within two (2) weeks prior to study entry
• Respiratory infection requiring medical attention, medical intervention or increase in supportive care of any manner within four (4) weeks prior to study entry
• Severe non-pulmonary/respiratory tract infection within four (4) weeks before study dosing or concomitant illness that in the opinion of the Principal Investigator (PI) creates unnecessary risks for gene transfer such as:
• Major renal or hepatic impairment
• Known seizure disorder
• Diabetes mellitus
• Idiopathic hypocalciuria
• Symptomatic cardiomyopathy
• History of bacterial meningitis or brain or spinal cord disease, including tumors, or abnormalities by magnetic resonance imaging (MRI) or computerized tomography (CT) that would interfere with the lumbar puncture (LP) procedures or CSF circulation
• Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
• Known allergy or hypersensitivity to iodine or iodine-containing products
• Concomitant use of any of the following: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy, plasmapheresis, immunomodulators such as adalimumab, or immunosuppressive therapy within 3 months of study dosing
• Inability to withhold use of laxatives or diuretics in the 24 hours prior to dose administration
• Anti-AAV9 antibody titers >1:50 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay
• Should a potential patient demonstrate anti AAV9 antibody titer > 1:50, he or she may receive retesting within 30 days of the screening period and will be eligible to participate if the anti AAV9 antibody titer upon retesting is ≤ 1:50
• Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin > 2 × ULN, creatinine ≥ 1.0 mg/dL, hemoglobin [Hgb] < 8 or > 18 g/dL; white blood cell [WBC] > 20,000 per cmm) prior to gene replacement therapy. Patients with an elevated bilirubin level that is unequivocally the result of neonatal jaundice shall not be excluded
• Participation in recent SMA treatment clinical trial or receipt of an investigational or approved compound product or therapy received with the intent to treat SMA at any time prior to screening for this study
• Oral beta agonists must be discontinued 30 days prior to dosing.
• Inhaled albuterol specifically prescribed for the purposes of respiratory (bronchodilator) management is acceptable and not a contraindication at any time prior to screening for this study
• Expectation of major surgical procedures during the 1-year study assessment period

• Have a diagnosis of migraine with or without aura as defined by the IHS ICHD-3 guidelines (1.1 or 1.2 according to ICHD-3 [2018]), with a history of migraine headaches of at least 6 months prior to screening.
• Participants who are taking, or are expected to take, therapeutic antibodies during the course of the study (adalimumab, infliximab, trastuzumab, bevacizumab, etc.). Prior use of therapeutic antibodies, other than antibodies to calcitonin gene-related peptide (CGRP) or its receptor, is allowed if that use was more than 12 months prior to baseline.
• Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to galcanezumab or its excipients.
• Current use or prior exposure to galcanezumab, another CGRP antibody, or CGRP receptor antibody, including those who have previously completed or withdrawn from this study or any other study investigating a CGRP antibody.
• History of persistent daily headache, cluster headache or migraine subtypes including hemiplegic (sporadic or familial) migraine and migraine with brainstem aura (previously basilar-type migraine) as defined by IHS ICHD-3.
• History of significant head or neck injury within 6 months prior to screening; or traumatic head injury at any time that is associated with significant change in the quality or frequency of their headaches, including new onset of migraine following traumatic head injury.
• Participants with a known history of intracranial tumors or developmental malformations including Chiari malformations.

• 18-80 years old
• Severe renal impairment (CrCl < 30 mL/min)
• Undergoing non-emergent surgery that requires neuromuscular blockade
• Planned extubation in the operating room immediately after surgery
• American Society of Anesthesiologists (ASA) physical status classification 3 to 4
• Willing and able to consent in English or Spanish
• No personal history of neuromuscular disease
• Age less than 18 or older than 80
• Patient does not speak English or Spanish
• Planned postoperative intubation/ventilation
• Allergy to sugammadex, neostigmine, glycopyrrolate, cisatracurium, or rocuronium
• Family or personal history of malignant hyperthermia
• Patient refusal
• Pregnant or nursing women
• "Stat" (emergent) cases
• Pre-existing muscle weakness of any etiology
• Patients on toremifene (a selective estrogen receptor modulator)
• Women on oral contraceptives who do not wish to use a non-hormonal method of contraception for 7 days following surgery

• Completion of study SOBI003-001
• Informed consent obtained from the patient´s legally authorized representative
• If, in the opinion of the investigator, there are patient specific safety concerns that contraindicates further treatment with SOBI003

• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patient is suspected of having localized newly-diagnosed HGG, excluding metastatic disease
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Patient and/or their parents or legal guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
• PRE-ENROLLMENT ELIGIBILITY SCREENING (STEP 0): Specimens obtained at the time of diagnostic biopsy must be submitted through APEC14B1 as soon as possible (ASAP), preferably within 13 calendar days of the procedure.
• Patients must be >= 3 years and =< 21 years of age at the time of enrollment
• Patients must have eligibility confirmed by Rapid Central Pathology and Molecular Screening Reviews performed on APEC14B1
• Newly diagnosed high-grade glioma with BRAFV600-mutation
• Positive or negative results for H3 K27M by immunohistochemistry (IHC)
• Histologically confirmed high-grade glioma (World Health Organization [WHO] grade III or IV) including but not limited to: anaplastic astrocytoma (AA), anaplastic pleomorphic xanthoastrocytoma (aPXA), anaplastic gangliogliomas (aGG), glioblastoma (GB), and high-grade astrocytoma, not otherwise specified (NOS)
• Patients must have had histologic verification of a high-grade glioma diagnosis. Cerebrospinal fluid (CSF) cytology by lumbar puncture must be done if clinically indicated and determined to be safe prior to study enrollment. If cytology proves positive, the patient would be considered to have metastatic disease and would, therefore, be ineligible.
• A pre- and post-operative brain magnetic resonance imaging (MRI) with and without contrast and a baseline spine MRI with contrast must be obtained prior to enrollment. The requirement for a post-operative MRI is waived for patients who undergo biopsy only. If the spine MRI is positive, the patient would be considered to have metastatic disease and would be ineligible.
• Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age.
• Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to enrollment).
• Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to enrollment).
• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions) (within 7 days prior to enrollment).
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) or
• A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
• Age 3 to < 6 years (Male 0.8 mg/dL, Female 0.8 mg/dL)
• Age 6 to < 10 years (Male 1 mg/dL, Female 1 mg/dL)
• Age 10 to < 13 years (Male 1.2 mg/dL, Female 1.2 mg/dL)
• Age 13 to 16 < years (Male 1.5 mg/dL, Female 1.4 mg/dL)
• Age >= 16 years (Male 1.7 mg/dL, Female 1.4 mg/dL)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment), and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L.
• Patients with a seizure disorder may be enrolled if their seizures are well controlled while on non-enzyme inducing anticonvulsants permitted on this study.
• Patients must be enrolled and protocol therapy must be projected to begin no later than 31 days after definitive surgery (day 0). If a biopsy only was performed, the biopsy date will be considered the date of definitive surgery. For patients who have a biopsy or incomplete resection at diagnosis followed by additional surgery, the date of the last resection will be considered the date of definitive surgery.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
• Patients with intrinsic brainstem or primary spinal cord tumors will be excluded.
• Patients with metastatic disease (defined as neuraxis dissemination either by imaging or by cytology) will be excluded.
• Patients must not have received any prior tumor-directed therapy including chemotherapy, radiation therapy, immunotherapy, or bone marrow transplant for the treatment of HGG other than surgical intervention and/or corticosteroids.
• Previous treatment with dabrafenib or another RAF inhibitor, trametinib or another MEK inhibitor, or an ERK inhibitor.
• Patients with a history of a malignancy with confirmed activating RAS mutation.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to dabrafenib, trametinib, and their excipients.
• Uncontrolled medical conditions (e.g., diabetes mellitus, hypertension, liver disease, or uncontrolled infection), psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol.
• Presence of active gastrointestinal (GI) disease or other condition (e.g., small bowel or large bowel resection) that will interfere significantly with the absorption of drugs.
• History of hepatitis B virus, or hepatitis C virus infection (patients with laboratory evidence of cleared hepatitis B virus and/or hepatitis C virus may be enrolled).
• History or current diagnosis of cardiac disease indicating significant risk of safety for patients participating in the study such as uncontrolled or significant cardiac disease, including any of the following:
• Recent myocardial infarction (within the last 6 months);
• Uncontrolled congestive heart failure;
• Unstable angina (within last 6 months);
• Clinically significant (symptomatic) or known, uncontrolled cardiac arrhythmias (e.g., sustained ventricular tachycardia, and clinically significant second or third degree atrioventricular [AV] block without a pacemaker) except sinus arrhythmia within the past 24 weeks prior to the first dose of study treatment;
• Coronary angioplasty or stenting (within last 6 months);
• Intra-cardiac defibrillators;
• Abnormal cardiac valve morphology (>= grade 2) documented by echocardiogram.
• Patients with a history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension).
• Patients with presence of interstitial lung disease or pneumonitis.
• Female patients who are pregnant are ineligible since there is yet no available information regarding human fetal or teratogenic toxicities.
• Lactating females are not eligible unless they have agreed not to breastfeed their infants for the duration of the study and for 4 months following discontinuation of study therapy.
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained.
• Sexually active patients of reproductive potential (male or female) are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 4 months following discontinuation of study therapy. Male patients (including those who have had a vasectomy) taking dabrafenib and trametinib combination therapy must use a condom during intercourse while on study and for 16 weeks after stopping treatment, and should not father a child during these periods. Women of childbearing potential should use effective non-hormonal contraception during therapy and for 4 weeks following discontinuation of dabrafenib and at least 4 months following the last dose of trametinib in patients taking combination therapy. Women should be advised that dabrafenib may decrease the efficacy of hormonal contraceptives and an alternate method of contraception, such as barrier methods, should be used.

Patients who meet the following inclusion criteria will be eligible for enrollment in the study: 1. Age between 18 and 60 years, inclusive. 2. Diagnosis of relapsing forms of MS, to include RRMS and active SPMS, diagnosed with McDonald Criteria 2005, 2010, and/or 2017 (1-3) 3. EDSS 0
•5.5 (Functional system changes in cerebral (or mental) functions and in bowel and bladder functions not used in determining EDSS for protocol eligibility). 4. Has had a minimum of 12 months of continuous natalizumab therapy (300 mg/d), including patients receiving extended interval dosing of natalizumab (e.g., less frequently than every-4-week infusion). 5. Negative history for any relapses at least 28 days prior to enrollment. 6. Weighing between 40 kilograms or more. 7. Female subjects of childbearing potential must use effective methods of contraception to prevent pregnancy for 4 weeks before initiation of cladribine tablets and must agree to continue to practice adequate contraception for at least 6 months after the last dose. Women using systemically acting hormonal contraceptives should add a barrier method during cladribine treatment and for at least 4 weeks after the last dose in each treatment year. 8. Female subjects must not be pregnant; female subjects must not be lactating or breast-feeding at least 10 days after the last dose. 9. Male subjects must be willing to use a condom during dosing and for six months after the last dose. Alternatively, their female partner must use another form of contraception (such as an intra-uterine device [IUD], barrier method with spermicide, or hormonal contraceptive [e.g., implant, injectable, patch or oral]) during dosing and for six months after last dose. 10. Understands and is capable of following through with study protocol requirements and assessments. 11. Willing to provide voluntary and informed consent based on the Health Insurance Portability and Accountability Act (HIPPA). Patients who meet any of the following exclusion criteria will not be eligible for enrollment in the study: 1. Natalizumab failure based on clinician's discretion. 2. Not active progressive MS (4). 3. A diagnosis of PML or any suspicion of PML. 4. A diagnosis of Clinically Isolated Syndrome 5. Known hypersensitivity to cladribine. 6. Any prior exposure to cladribine. 7. Lymphocyte count not within normal limits of the local, hospital laboratory. 8. Previous or current exposure to mitoxantrone, azathioprine, methotrexate, cyclophosphamide, myelosuppressive treatments, total lymphoid irradiation. 9. Receiving oral or systemic corticosteroid treatments within the 28 days prior to enrollment. 10. Receiving cytokine base treatment, Intra Venous Immuno Globulin (IVIG) or Plasma pheresis, 3 months prior to enrollment in the study. 11. Having platelet count or neutrophil count below the lower limit of the normal range within the 28 days prior to enrollment in the study. 12. Positive for HIV, or positive hepatitis C antibody test or hepatitis B surface antigen test and/or core antibody test for IgG and/or IgM. 13. History of tuberculosis (TB), presence of active tuberculosis, or latent tuberculosis as detected by local standard of practice like imaging (e.g., chest X-ray, chest CT scan, MRI) and/or positive QuantiFERON-TB Gold test and/or skin test and/or clinical examination or has had latent TB disease at any time in the past. 14. Immunocompromised subjects, including subjects currently receiving immunosuppressive or myelosuppressive therapy with, e.g., monoclonal antibodies, methotrexate, cyclophosphamide, cyclosporine or azathioprine, or chronic use of corticosteroids. 15. Active malignancy or history of malignancy. 16. Received a live vaccine within 6 weeks prior to cladribine tablet administration or intends to receive a live vaccination during the trial. After the last dose of cladribine tablets, the subject should avoid live vaccine as long as the subject's white blood cell counts are not within normal limits. 17. Allergy or hypersensitivity to gadolinium and/or any other contraindication to perform an MRI. 18. Has any renal condition that would preclude the administration of gadolinium (e.g. acute or chronic severe renal insufficiency (GFR < 30 mL/min/1.73m2) -

1. At least 18 years of age and up to 55 years (inclusive) of age at Baseline. 2. Clinical diagnosis of Multiple Sclerosis (MS) who have had Relapsing MS (RMS) no longer than 15 years from diagnosis. 3. Stable treatment with natalizumab for at least the prior six (6) months. 4. Stable disease activity over the prior six (6) months. 5. All hematological parameters and biochemical parameters deemed stable or transient in nature. 6. Able to understand and give written informed consent. 1. Patients with a clinical relapse requiring systemic steroid treatment within the prior six (6) months. 2. Patients treated with any other MS therapy other than natalizumab; or treated with clemastine fumarate. 3. Patients with a history of significant other major medical condition that may interfere with the conduct of the study or interpretation of the study results. 4. Patients who may have difficulty complying with the protocol and/or study procedures. 5. Patient with clinically significant abnormalities in hematology, blood chemistry, ECG, or physical examination not resolved by the Baseline visit which according to Investigator can interfere with study participation. 6. Patients with clinically significant hepatic or renal dysfunction or clinical laboratory findings that would limit the interpretability of change in liver or kidney function, or those with low platelet counts (< 150 x 109 per liter) or eosinophilia (absolute eosinophil count of ≥500 eosinophils per microliter). 7. Patients with a prior history of, or positive serological assay for the presence of HIV infection, or laboratory evidence of active or chronic infection with hepatitis C (HCV) or hepatitis B (HBV). 8. Patients participating in any other investigational drug trial or using an investigational drug (within 12 weeks prior to screening and thereafter) 9. Positive screen for drugs of abuse or known alcohol abuse. 10. Females who are pregnant, have a positive pregnancy test, are nursing, or who plan to get pregnant during the course of this clinical trial or within 6 months of the end of this trial. 11. Women of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control during the study and for 6 months following completion of study participation. 12. Patients with implanted metal objects in their body that may be affected by an MRI procedure. 13. Patients who are claustrophobic or otherwise unlikely to be able to complete the MRI scanning procedures. 14. Patients with a history of gold allergy. 15. Patient is considered a suicide risk in the opinion of the Investigator, has previously made a suicide attempt, or is currently demonstrating active suicidal ideation. 16. Any active ophthalmological cause for retinal damage other than MS or based on the Investigator's judgment any other ophthalmic diseases that would confound the study results or optical coherence tomography assessment. 17. PRN use of stimulant medications including: amphetamine, dextroamphetamine, lisdexamfetamine, methylphenidate, or modafinil.

• Age 50 and older
• Native English speakers
• 12 years of education or higher
• Active diagnosis of aMCI
• History of TBI based on VA/DOD criteria
• TBI within the past 2 years
• Lifetime history of stroke, transient ischemic attack, heart attack, or congestive heart failure
• Lifetime history of epilepsy
• Major psychiatric disorders (i.e., posttraumatic stress disorder, bipolar disorder, schizophrenia)
• Substance use disorder
• Has metal fragments in head
• Taking medications that may interact with the HD-tDCS effect (i.e., amphetamines, L-dopa, carbamazepine, sulpiride, pergolide, lorazepam, dextromethorphan, D-cycloserine, flunarizine, or ropinirole)

1. Participant is able and willing to provide informed consent (≥18 years), or informed consent is obtained by the parent or legal guardian for minor participants, with the minor providing age appropriate assent, according to local law and regulations; 2. Life expectancy ≥ 12 weeks; 3. Known high-risk neuroblastoma with failure to respond to standard therapy (combination chemotherapy with or without radiation and surgery), or development of PD at any time; 4. Adequate recovery from acute toxic effects of any prior therapy, as deemed by the Investigator or treating Sub-Investigator; 5. Adequate liver function as defined by the following laboratory values obtained within 28 days prior to administration of 64Cu-SARTATE: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 x upper limit of normal (ULN); 6. Adequate renal function; 7. Adequate laboratory parameters: Absolute neutrophil count > 1.0 x 109/L; Platelet count > 50 x 109/L; Serum bilirubin <1.5 x ULN; 8. Karnofsky or Lansky performance status ≥50; 9. All participants must have a hematopoietic stem cell product available (minimum CD34+ cell dose is ≥2 x 106 cells/kg); 10. Sexually active participants of reproductive potential must practice an effective method of birth control while participating on this study, to avoid possible damage to the fetus. Abstinence is considered acceptable; 11. 64Cu-SARTATE uptake on the 4 hour scan (SUVmax) of any lesion equal to or higher than that of the liver in order to move on to the therapy phase of the study. 1. Participants with disease of any major organ system that would compromise their ability to tolerate therapy, as deemed by the Investigator or treating Sub-Investigator; 2. Any other active malignancy, or a history of prior malignancy within the past 3 years; 3. History of cardiac failure as evidenced by: dyspnea at rest, exercise intolerance, oxygen requirement, clinically significant cardiac dysfunction; 4. Planned administration of chemotherapy, anti-cancer cytokine therapy, immunotherapy, radiotherapy or other investigational agents within 2 weeks prior to the administration of 64Cu-SARTATE and 4 weeks prior to the administration of 67Cu-SARTATE; 5. Administration of therapeutic dose of 131I-MIBG within 8 weeks prior to the administration of 64Cu-SARTATE; 6. EBRT to both kidneys or a single functioning kidney within 12 months prior to the administration of 64Cu-SARTATE; 7. Administration of any investigational agents within 28 days prior to administration of 64Cu-SARTATE; 8. Treatment with long acting somatostatin analogues (administered within 28 days prior to the administration of 64Cu-SARTATE), or short acting somatostatin analogues (administered within 24 hours prior to the administration of 64Cu-SARTATE); 9. Known sensitivity or allergy to somatostatin analogues; 10. Previous PRRT; 11. Female participants who are pregnant or lactating; 12. Participants who are on hemodialysis; 13. QTc interval ≥ 0.45 seconds as measured by Screening ECG; 14. Participants with uncontrolled infection(s); 15. Any medical condition which the Investigator feels may interfere with the procedures or evaluations of the study; 16. Participants 12 month and younger will be excluded from cohorts where the planned single or cumulative administered activity is modelled to deliver a radiation dose to the marrow that exceeds 2 Gy.

• Diagnosis of glucose transporter type 1 deficiency (G1D), confirmed by clinical genotyping at a CLIA-certified laboratory.
• Stable on ketogenic diet at 2.5:1 to 4:1 ratio (i.e., no changes in ratio will have taken place for 2 months). The initiation of a ketogenic diet is previous to
•and thus is not part of this study.
• Males and females 30 months to 35 years and 11 months old inclusive.
• Subjects with evidence of independent, unrelated metabolic and/or genetic disease.
• Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome, crohn's disease, or colitis that could increase the subject's risk of developing diarrhea or stomach pain.
• Subjects with a BMI (body mass index) greater than or equal to 30.
• Subjects currently not on ketogenic diet.
• Women who are pregnant or breast feeding may not participate. Women who plan to become pregnant during the course of the study, or who are unwilling to use birth control to prevent pregnancy (including abstinence) may not participate. Females age 10 and over will be asked to provide a urine sample for a pregnancy test via dipstick. Subjects will be asked to agree to abstinence or another form of birth control for the duration of the study.
• Allergy/sensitivity to C7
• Previous use of triheptanoin less than 1 month prior to study initiation.
• Treatment with medium chain triglycerides in the last 24 hours.
• Subjects exhibiting signs of dementia, or diagnosed with any degenerative brain disorder (such as Alzheimer's disease) that would confound assessment of cognitive changes, in the opinion of the investigator.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Inability or unwillingness of subject or legal guardian/representative to give written informed consent, or assent for children age 10-17,
• Addition of a new antiseizure drug in the previous 3 months.

1. Adults 18 to 55 years of age on the day of injury, 2. Non-penetrating closed head trauma. 3. Glasgow Coma Score between (GCS) between 3 and 8, (best un-medicated post-resuscitation score during screening). 4. Ability to obtain legally authorized representative consent for participation and complete the BMMNC/Sham harvest and cell/placebo infusion within 48 hours of the initial injury. 5. Ability to speak English or Spanish. 1. Known history of: 1. previous brain injury, 2. intellectual deficiency or psychiatric condition likely to invalidate our ability to assess post-injury changes in cognition or behavior, 3. neurologic impairment and/or deficit, 4. seizure disorder requiring anti-convulsant therapy, 5. recently treated significant infection, 6. renal disease/altered renal function (post-resuscitation serum creatinine > 1.5 mg/dL), 7. chronic hepatic disease or altered liver function (post-resuscitation SGPT > 150 U/L, and/or T. Bilirubin >1.3 mg/dL), 8. cancer, 9. Chemical or ETOH dependency, 10. immunosuppression (admission WBC < 3X103), 11. HIV positive status; 2. Obliteration of perimesencephalic cistern on initial head CT/MRI suggesting prolonged hypoxic ischemic insult; 3. Initial hospital ICP > 40 mm Hg; 4. Hemodynamic instability at the time of screening defined as SBP < 90mmHg, ongoing fluid resuscitation and/or requirement for inotropic support to maintain MAP at or above normals for age
•does not include CPP based inotropic support; 5. Uncorrectable coagulopathy at the time of screening; 6. Unstable pelvic fractures that in the P.I.'s opinion would preclude the bone marrow / sham harvest; 7. Pulmonary contusions defined as a chest x-ray with non-anatomic opacification and PaO2:FiO2 ratio < 250 associated with the mechanism of injury; 8. Greater than AAST Grade III solid or hollow visceral injury of the abdomen and/or pelvis diagnosed by CT or other imaging; 9. Spinal cord injury diagnosed by CT or MR imaging or by clinical findings; 10. Persistent hypoxia defined as SaO2 < 94% for > 30 minutes occurring at any time from hospital admission to time of consent; 11. Positive pregnancy test (if applicable); 12. Concurrent participation in an interventional drug/device research study; 13. Unwillingness to return for follow-up visits; 14. Contraindications to MRI.

• All patients must have a pathologically confirmed diagnosis of neuroblastoma, ≤ 30.99 years of age with history of relapsed/refractory neuroblastoma.
• All patients must have completed upfront therapy with at least 4 cycles of aggressive multi-drug chemotherapy.
• Specific Criteria by Arm: Arms 1 and 2: Subjects with no active disease: i. No evidence of residual disease by CT/MRI and MIBG scan (or PET for patients who have a history of MIBG non-avid disease). o Note: Patients with residual masses detected by CT/MRI may be considered in CR if their MIBG is negative or if MIBG positive and evaluated by PET and found to have negative PET scans; biopsy confirmation may be considered if there is still reasonable concern for persistent disease but is not required. ii. No evidence of disease metastatic to bone marrow. Arm 3: Measurable or evaluable disease, including at least one of the following: Measurable tumor by CT or MRI; or a positive MIBG and PET; or positive bone marrow biopsy/aspirate in at least one site.
• Timing from prior therapy: Enrollment (first dose of DFMO) no later than 60 days from last dose of the most recent therapy.
• Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer chemotherapy and be within the following timelines: 1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study (6 weeks if prior nitrosourea). 2. Hematopoietic growth factors: At least 5 days since the completion of therapy with a growth factor. 3. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the Study Chair. 4. Immunotherapy: At least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells. 5. Anti-GD2 Monoclonal antibodies: At least 2 weeks must have elapsed since prior treatment with a monoclonal antibody. 6. XRT: At least 14 days since the last treatment except for radiation delivered with palliative intent to a non-target site. 7. Stem Cell Transplant: 1. Allogeneic: No evidence of active graft vs. host disease 2. Allo/Auto: ≥ 2 months must have elapsed since transplant. 8. MIBG Therapy: At least 8 weeks since treatment with MIBG therapy
• Subjects must have a Lansky or Karnofsky Performance Scale score of 60% or higher.
• Life expectancy > 2 months
• All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to first dose of study drug unless otherwise indicated below.
• Subjects must have adequate organ functions at the time of registration:
• Hematological: Total absolute neutrophil count ANC ≥750/μL
• Liver: Subjects must have adequate liver function as defined by AST and ALT <5x upper limit of normal (Normal=45), Bilirubin <1.5x upper limit normal (Normal=1.0). Normal PT, PTT, fibrinogen.
• Renal: Adequate renal function defined as (perform one of the following): Creatinine clearance or radioisotope GFR 70 mL/min/1.73 m2 or greater or a serum creatinine based on age/gender
• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
• Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or patients' legal representative).
• BSA of <0.25 m2.
• Subjects that received DFMO at a dose higher than 1000mg/m2 BID prior to this study are not eligible.
• Subjects that received a dose of DFMO in combination with etoposide are not eligible.
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

• Patients must be:
• < 12 months (< 365 days) of age at diagnosis with INRG stage L1; or
• < 18 months (< 547 days) of age at diagnosis with INRG stage L2 or stage Ms neuroblastoma/ganglioneuroblastoma
• Enrollment on ANBL00B1 or APEC14B1 is required for all newly diagnosed patients
• Patients must have newly diagnosed v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) non-amplified neuroblastoma (International Classification of Diseases for Oncology [ICD-O] morphology 9500/3) or MYCN non-amplified ganglioneuroblastoma verified by histology
• Patients must meet the specified criteria for one of the treatment groups defined below; genomic features include MYCN gene amplification, segmental chromosome aberrations (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) and deoxyribonucleic acid (DNA) index
• "Favorable" genomic features are defined by one or more whole-chromosome gains or hyperdiploid tumor (DNA index > 1) in the absence of segmental chromosome aberrations as defined above
• "Unfavorable" genomic features are defined by the presence of any segmental chromosome aberration (somatic copy number loss at 1p, 3p, 4p, or 11q or somatic copy number gain at 1q, 2p, or 17q) or diploid tumor (DNA index = 1); this includes copy neutral loss of heterozygosity (LOH)
• Only patients with MYCN non-amplified tumors are eligible for this study
• Group A: patients < 12 months (< 365 days) of age with newly diagnosed INRG stage L1 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• Greatest tumor diameter < 5 cm of adrenal or non-adrenal origin
• Patients with non-adrenal primaries are eligible, but must have positive uptake on metaiodobenzylguanidine (MIBG) scan or elevated catecholamine metabolites (urine or serum) to support the diagnosis of neuroblastoma
• No prior tumor resection or biopsy
• Group A will be further split into two subsets, which are mutually exclusive, for statistical purposes
• Group A1:
• > 6 months and < 12 months of age with an adrenal primary tumor < 5 cm in greatest diameter OR
• Patients less than 6 months of age with an adrenal primary tumor > 3.1 and < 5 cm in greatest diameter OR
• < 12 months of age with a non-adrenal primary site < 5 cm in greatest diameter
• Group A2: =< 6 months of age with an adrenal primary site and tumor =< 3.1 cm in greatest diameter.
• Group B: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage L2 neuroblastoma/ganglioneuroblastoma who meet the following criteria:
• No life threatening symptoms or no impending neurologic or other organ function compromise (e.g. epidural or intraspinal tumors with existing or impending neurologic impairment, periorbital or calvarial-based lesions with existing or impending cranial nerve impairment, anatomic or mechanical compromise of critical organ function by tumor [abdominal compartment syndrome, urinary obstruction, etc.]); horner syndrome is not considered neurologic compromise
• No prior tumor resection, tumor biopsy ONLY
• Only patients with both favorable histology and favorable genomic features will remain on study as part of Group B; the institution will be notified of histologic and genomic results within 3 weeks of specimen submission on ANBL00B1 or APEC14B1
• Group C: patients < 18 months (< 547 days) of age with newly diagnosed INRG stage Ms neuroblastoma/ganglioneuroblastoma
• No prior radiotherapy or chemotherapy, with the exception of dexamethasone, which is allowed
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients with MYCN amplified tumors are not eligible
• Group B and C patients who do not enroll on ANBL1232 within 4 weeks of definitive diagnostic procedure
• Group A and C patients, not required to undergo tumor biopsy, who do not enroll on ANBL1232 within 4 weeks of confirmatory imaging study

• Patient must be newly diagnosed or relapsed/progressed with a brain tumor that has not previously been treated with CRT
• Note: COG therapeutic study participation is not required for ACCL10P1 enrollment
• Patient enrollment must occur within 4 calendar months following completion of CRT
• Reminder: after patient enrollment, baseline testing followed by randomization must occur within 2-4 months after completion of CRT
• The patient must have an identified caregiver who is willing and able to oversee the training practice during the intervention period (ie, for 5-9 weeks starting approximately 3 months after completion of CRT)
• The patient must have access to a telephone and phone number where they can be reached
• The patient and caregiver must have reading, speaking and listening comprehension of English
• All patients and/or their parents or legal guardians must sign a written informed consent (patient assent is also recommended when applicable according to each institution's policy)
• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
• Patients with pontine glioma are not eligible
• Patients with an estimated survival of less than one year are not eligible
• Patients with a history of traumatic brain injury prior to tumor diagnosis are not eligible
• Patients with a motor, visual, or auditory handicap that prevents computer use (e.g., unresolved posterior fossa syndrome) are not eligible to participate in this trial
• Patients with full-scale intelligence quotient (IQ) < 70 per previous testing OR existing diagnosis of/educational classification as a student with an intellectual disability are not eligible

• Younger than 2 years (chronological age)
• Scheduled for anaesthesia that is expected to last at least 2 hours (and/or total operating room time is scheduled to be at least 2.5 hours)
• Has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf.
• Known neurologic, chromosomal or congenital anomaly which is likely to be associated with poor neurobehavioural outcome
• Existing diagnosis of behavioural or neurodevelopmental disability
• Prematurity (defined as < 36 weeks gestational age at birth)
• Birth weight less than 2 kg.
• Congenital cardiac disease requiring surgery
• Intracranial neurosurgery and intracranial craniofacial surgery (isolated cleft lip is not an exclusion)
• Previous cumulative exposure to general anaesthesia exceeding 2 hours
• Planned future cumulative exposure to anaesthesia exceeding 2 hours before the age of 3 years.
• Any specific contra-indication to any aspect of the protocol
• Previous adverse reaction to any anaesthetic
• Circumstances likely to make long term follow-up impossible
• Living in a household where the primary language spoken at home is not a language in which we can administer the Wechsler Preschool and Primary School Intelligence Scale
• Planned postoperative sedation with any agent except opioids (e.g. benzodiazepines, dexmedetomidine, ketamine, barbiturates, propofol, clonidine, chloral hydrate, and other non-opioid sedatives). For example if such sedation is planned for post-operative ventilation

Inclusion criteria: Patients with Pompe disease who previously completed a neoGAA study. The patient and/or their parent/legal guardian is willing and able to provide signed informed consent, and the patient, if <18 years of age, is willing to provide assent if deemed able to do so. The patient (and patient's legal guardian if patient is <18 years of age) must have the ability to comply with the clinical protocol. The patient, if female and of childbearing potential, must have a negative pregnancy test [urine beta-human chorionic gonadotropin] at baseline. Exclusion criteria: The patient is concurrently participating in another clinical study using investigational treatment. The patient, in the opinion of the Investigator, is unable to adhere to the requirements of the study. The patient has clinically significant organic disease (with the exception of symptoms relating to Pompe disease), including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, precludes participation in the study or potentially decreases survival. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• All patients must have a pathologically confirmed diagnosis of neuroblastoma, < 30.99 years of age and classified as high risk at the time of diagnosis. Exception: patients who are initially diagnosed as non-high-risk neuroblastoma, but later converted (and/or relapsed) to high risk neuroblastoma are also eligible.
• All patients must be in complete remission (CR): 1. No evidence of residual disease on scan 2. No evidence of disease metastatic to bone marrow.
• Specific Criteria by Stratum: Stratum 1/1B: All patients must have completed standard upfront therapy that replicates treatment which patients who were enrolled on ANBL0032 received, including: intensive induction chemotherapy and (if feasible) resection of primary tumor, followed by: consolidation with high-dose chemotherapy with stem cell transplant and radiotherapy, followed by: immunotherapy with Ch14.18/IL-2/GM-CSF (dinutuximab) and retinoic acid;. All subjects on Stratum 1/B must have also met the following criteria: • A pre-transplant disease status evaluation that met International Neuroblastoma Response Criteria (INRC) for CR (complete response), VGPR (very good partial response), or PR (partial response) for primary site, soft tissue metastases and bone metastases. Patients who meet those criteria must also meet the protocol-specified criteria for bone marrow response prior to transplant as outlined below: No more than 10% tumor involvement (based on total nucleated cellular content) seen on any specimen from a bilateral bone marrow aspirate/biopsy. Stratum 2: Neuroblastoma that is in first complete remission following standard upfront therapy different from that described for Stratum 1. Stratum 3: Neuroblastoma that failed to have a response of at least PR following induction chemotherapy and surgical resection of the primary tumor, but that has achieved CR following additional therapy. Stratum 4: Patients who have achieved a second or subsequent CR following relapse(s).
• Pre-enrollment tumor survey: Prior to enrollment on this study, a determination of mandatory disease staging must be performed:
• Tumor imaging studies including
• Bilateral bone marrow aspirates and biopsy
• This disease assessment is required for eligibility and preferably should be done within 2 weeks prior to enrollment, but must be done within a maximum of 4 weeks before enrollment.
• Timing from prior therapy: Stratum 1/1B: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy. Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy.
• Patients must have a Lansky or Karnofsky Performance Scale score of > 50% and patients must have a life expectancy of ≥ 2 months.
• All clinical and laboratory studies for organ functions to determine eligibility must be performed within 7 days prior to enrollment unless otherwise indicated below.
• Patients must have adequate organ functions at the time of registration:
• Hematological: Total absolute phagocyte count ≥1000/μL
• Liver: Subjects must have adequate liver function
• Renal: Adequate renal function
• Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
• Written informed consent in accordance with institutional and FDA (food and drug administration) guidelines must be obtained from all subjects (or patients' legal representative).
• BSA (Body Surface Area) of <0.25 m2.
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from hematological and bone marrow suppression effects of prior chemotherapy.
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

1. Subject's parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization, where applicable, prior to any study-related procedures; participants will be asked to give written or verbal assent according to local requirements 2. Subject has a centrally confirmed (by TRiNDS central genetic counselor[s]) diagnosis of DMD as defined as:
• Dystrophin immunofluorescence and/or immunoblot showing complete dystrophin deficiency, and clinical picture consistent with typical DMD, OR
• Identifiable mutation within the DMD gene (deletion/duplication of one or more exons), where reading frame can be predicted as 'out-of-frame,' and clinical picture consistent with typical DMD, OR
• Complete dystrophin gene sequencing showing an alteration (point mutation, duplication, other) that is expected to preclude production of the dystrophin protein (i.e., nonsense mutation, deletion/duplication leading to a downstream stop codon), with a clinical picture consistent with typical DMD; 3. Subject is ≥ 4 years and <7 years of age at time of enrollment in the study; 4. Subject weighs >13.0 kg and ≤ 39.9 kg at the Screening Visit; 5. Subject is able to walk independently without assistive devices; 6. Subject is able to complete the Time to Stand Test (TTSTAND) without assistance in <10 seconds, as assessed at the Screening Visit; 7. Clinical laboratory test results are within the normal range at the Screening Visit, or if abnormal, are not clinically significant, in the opinion of the Investigator. [Notes: Serum gamma glutamyl transferase (GGT), creatinine, and total bilirubin all must be ≤ upper limit of the normal range at the Screening Visit. An abnormal vitamin D level that is considered clinically significant will not exclude a subject from randomization]; 8. Subject has evidence of chicken pox immunity as determined by:
• Presence of IgG antibodies to varicella, as documented by a positive test result from the local laboratory from blood collected during the Screening Period, OR
• Documentation, provided at the Screening Visit, that the subject has had 2 doses of varicella vaccine, with or without serologic evidence of immunity; the second of the 2 immunizations must have been given at least 14 days prior to randomization. 9. Subject is able to swallow tablets, as confirmed by successful test swallowing of placebo tablets during the Screening Period; and 10. Subject and parent(s)/guardian(s) are willing and able to comply with scheduled visits, study drug administration plan, and study procedures. 1. Subject has current or history of major renal or hepatic impairment, diabetes mellitus or immunosuppression; 2. Subject has current or history of chronic systemic fungal or viral infections; 3. Subject has had an acute illness within 4 weeks prior to the first dose of study medication; 4. Subject has used mineralocorticoid receptor agents, such as spironolactone, eplerenone, canrenone (canrenoate potassium), prorenone (prorenoate potassium), mexrenone (mexrenoate potassium) within 4 weeks prior to the first dose of study medication; 5. Subject has a history of primary hyperaldosteronism; 6. Subject has evidence of symptomatic cardiomyopathy [Note: Asymptomatic cardiac abnormality on investigation would not be exclusionary]; 7. Subject is currently being treated or has received previous treatment with oral glucocorticoids or other immunosuppressive agents [Notes: Past transient use of oral glucocorticoids or other oral immunosuppressive agents for no longer than 1 month cumulative, with last use at least 3 months prior to first dose of study medication, will be considered for eligibility on a case-by-case basis, unless discontinued for intolerance. Inhaled and/or topical glucocorticoids are permitted if last use is at least 4 weeks prior to first dose of study medication or if administered at stable dose beginning at least 4 weeks prior to first dose of study medication and anticipated to be used at the stable dose regimen for the duration of the study]; 8. Subject has an allergy or hypersensitivity to the study medication or to any of its constituents; 9. Subject has used idebenone within 4 weeks prior to the first dose of study medication; 10. Subject has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the Investigator; 11. Subject has previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow-up will be correctly completed or impair the assessment of study results, in the opinion of the Investigator; 12. Subject is taking (or has taken within 4 weeks prior to the first dose of study medication) herbal remedies and supplements which can impact muscle strength and function (e.g., Co-enzyme Q10, creatine, etc); 13. Subject is taking (or has taken within 3 months prior to the first dose of study medication) any medication indicated for DMD, including Exondys51 and Translarna; 14. Subject has been administered a live attenuated vaccine within 14 days prior to the first dose of study medication; 15. Subject is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of study medication; 16. Subject has a sibling who is currently enrolled in any vamorolone study or Expanded Access Program, or who intends to enroll in any vamorolone study or Expanded Access Program during the subject's participation in the VBP15-004 study; or 17. Subject has previously been enrolled in the study. Note: Any parameter/test may be repeated at the Investigator's discretion during Screening to determine reproducibility. In addition, subjects may be rescreened if ineligible due to a transient condition which would prevent the subject from participating, such as an upper respiratory tract infection or injury, or if ineligible due to negative anti-varicella IgG antibody test result.

1. Age 18 or greater 2. Able to obtain informed consent from patient or appropriate designee 3. Possible autoimmune encephalitis as defined by Table 1: 1. Reasonable exclusion of alternative causes 2. Subacute onset (< 3 months) of memory deficits, altered consciousness, and/or psychiatric symptoms 3. One or more of the following:
• CSF (cerebrospinal fluid) pleocytosis (>5 cells/µl corrected, if necessary, for traumatic lumbar puncture)
• EEG (electroencephalogram) with epileptiform or focal slow wave abnormalities involving temporal lobes
• Brain abnormalities on T2/FLAIR MRI restricted to the mesial temporal (limbic) lobes
• Associated dyskinesias (faciobrachial dystonic movements or orofacial dyskinesias) 4. Completed initial treatment with iv steroids (at least 3000mg solumedrol) and plasma exchange (at least 3 exchanges) within the past 8 weeks 5. Presence of one (or more) of the following autoantibodies in serum or CSF
• NMDA receptor
• LGI1
• CASPR2
• DPPX 1. Prior immunosuppression treatment in past year (other than steroids, intravenous immunoglobulin and plasma exchange) 2. Active malignancy requiring chemotherapy 3. Pregnancy 4. Evidence of active hepatitis or tuberculosis infection 5. Medical condition that (in investigators opinion) precludes the use of ocrelizumab

• Has completed a study of SRP-5051 and continues to meet the Eligibility Criteria of Study 5051-102.
• Initiation or change of dosing (except for modifications to accommodate changes in weight or changes in standard of care) since completing a study administering SRP-5051 and while participating in this study for any of the following: angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocking agents (ARBs), beta-blockers, potassium and steroids*.
• Requires antiarrhythmic and/or diuretic therapy for heart failure.
• Use of any herbal medication/supplement containing aristolochic acid.
• Treatment with any experimental therapy since entering original study or any experimental gene therapy for the treatment of DMD at any time.
• Participation in an interventional clinical trial since completing original study. Other inclusion/exclusion criteria apply. * The dose of steroids must remain constant except for modifications to accommodate changes in weight.

1. At least 18 years of age 2. Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee 3. Histologically confirmed glioma 4. Progression by RANO criteria following standard treatment options with known survival benefit (Temozolomide, Radiation, and Tumor Treating Fields [unless unwilling]) 5. Patients who receive treatment with antiepileptic medications must have a two week history of stable dose of antiepileptic without seizures prior to dosing 6. Patients with corticosteroid requirements to control cerebral edema must be maintained at a stable or decreasing dose for a minimum of two weeks without progression of clinical symptoms 7. A volume of enhancing tumor which falls within the treatment field volume being evaluated in the respective cohort (see 4.1 Design) 8. ECOG performance status of 0 to 2 9. Life expectancy of at least 2 months 10. Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal
• AST (SGOT) and ALT (SGPT) ≤ 3.0 times upper limit of normal (ULN); 11. Acceptable renal function:
• Serum creatinine ≤1.5xULN 12. Acceptable hematologic status (without hematologic support):
• ANC ≥1000 cells/uL
• Platelet count ≥100,000/uL
• Hemoglobin ≥9.0 g/dL 13. All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose For part 2: 14. Bevacizumab naïve glioblastoma with no more than 1 recurrence 1. The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible. 2. The subject is unable to undergo MRI scan (eg, has pacemaker). 3. The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study. 4. The subject is pregnant or breast-feeding. 5. The subject has serious intercurrent illness, as determined by the treating physician, that would compromise either patient safety or study outcomes such as:
• hypertension (two or more blood pressure readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment
• Non-healing wound, ulcer, or bone fracture
• Clinically significant cardiac arrhythmias
• Untreated hypothyroidism
• Uncontrolled systemic infection
• Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug
• Myocardial infarction, stroke, transient ischemic attack within 6 months
• Known active malignancy (other than glioma) except non-melanoma skin cancer or carcinoma in-situ in the cervix 6. The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding 7. The subject has received any of the following prior anticancer therapy:
• Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy, or intra-operative radiotherapy (IORT) to the target site.
• Radiation therapy within 12 weeks of screening
• Systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 14 days or 5 half-lives, whichever is shorter, prior first dose of study drug
• Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
• Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug
• Prior treatment with carmustine wafers
• Patients who are currently receiving any other investigational agents and/or who have received an investigational agent in the prior 28 days 8. Multifocal progression or involvement of the leptomeninges 9. Psychiatric illness/social situations that would limit compliance with the study requirements 10. Infratentorial disease

• Infants born with postmenstrual age less than 28 weeks
• Signed informed consent, unless the NICU has chosen to use 'opt-out' or deferred consent as consent method.
• Missing written parental informed consent (if the 'opt-out' method is used for consent, lack of a record that the clinical staff have explained the trial and the 'opt-out' consent process to parents and/or a record in the infant's clinical file of parents' decision to opt-out, are exclusion criteria)
• Decision not to conduct full life support
• No possibility to place cerebral NIRS oximeter within six hours after birth

• Non-penetrating traumatic brain injury
• Glasgow Coma Scale (GCS) 3-8 measured off paralytics
• Glasgow Coma Scale motor score < 6 if endotracheally intubated
• Evidence of intracranial trauma on CT scan
• Able to place intracranial probes and randomize within 6 hours of arrival at enrolling hospital
• Able to place intracranial probes and randomize within 12 hours from injury
• Age greater than or equal to 14 years
• Non-survivable injury
• Bilaterally absent pupillary response in the absence of paralytic medication
• Contraindication to the placement of intracranial probes
• Treatment of brain tissue oxygen values prior to randomization
• Planned use of devices which may unblind treating physicians to brain tissue hypoxia
• Systemic sepsis at screening
• Refractory hypotension
• Refractory systemic hypoxia
• PaO2/FiO2 ratio < 200
• Known pre-existing neurologic disease with confounding residual neurological deficits
• Known inability to perform activities of daily living (ADL) without assistance prior to injury
• Known active drug or alcohol dependence that, in the opinion of site investigator, would interfere with physiological response to brain tissue oxygen treatments
• Pregnancy
• Prisoner
• On EFIC Opt-Out list as indicated by a bracelet or medical alert

• Patients must have had histologic verification of juvenile myelomonocytic leukemia (JMML) at original diagnosis and currently have relapsed or refractory disease; the diagnosis is made based on the following criteria
• JMML category 1 (all of the following): the diagnostic criteria must include all features in category 1 and EITHER (i) one of the features in category 2 OR (ii) two features from category 3 to make the diagnosis
• Splenomegaly
• > 1000 (1 x 10^9/uL) circulating monocytes
• < 20% blasts in the bone marrow or peripheral blood
• Absence of the t(9;22) or BCR/ABL fusion gene
• JMML category 2 (at least one of the following if at least two category 3 criteria are not present):
• Somatic mutation in RAS or PTPN11
• Clinical diagnosis of NF1 or NF1 gene mutation
• Homozygous mutation in CBL
• Monosomy 7
• JMML category 3 (at least two of the following if no category 2 criteria are met):
• Circulating myeloid precursors
• White blood cell count, > 10 000 (10 x 10^9/ uL)
• Increased hemoglobin F for age
• Clonal cytogenetic abnormality
• GM-CSF hypersensitivity
• Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes of any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to AML at any point with more than 20% blasts are not eligible for this trial
• Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
• Myelosuppressive chemotherapy: patients must have completely recovered from all acute toxic effects of chemotherapy, immunotherapy or radiotherapy prior to study enrollment; at least 14 days must have elapsed since the completion of cytotoxic therapy, with the exception of hydroxyurea
• Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of protocol therapy
• Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
• Biologic (anti-neoplastic agent): at least 7 days must have elapsed since completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
• Monoclonal antibodies:
• At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines
• At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
• Radiotherapy:
• >= 2 weeks must have elapsed since local palliative external radiation therapy (XRT) (small port)
• >= 6 months must have elapsed if prior craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if traumatic brain injury (TBI) was received
• >= 4 weeks must have elapsed if other substantial bone marrow irradiation was given
• Stem cell transplant or rescue without TBI: no evidence of active graft versus (vs.) host disease and >= 3 months must have elapsed since transplant; >= 4 weeks must have elapsed since any donor lymphocyte infusion
• Patients must not be known to be refractory to red blood cell or platelet transfusions
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
• Age: Maximum serum creatinine (mg/dL)
• 1 month to < 6 months: 0.4 (male) 0.4 (female)
• 6 months to < 1 year: 0.5 (male) 0.5 (female)
• 1 to < 2 years: 0.6 (male) 0.6 (female)
• 2 to < 6 years: 0.8 (male) 0.8 (female)
• 6 to < 10 years: 1 (male) 1 (female)
• 10 to < 13 years: 1.2 (male) 1.2 (female)
• 13 to < 16 years: 1.5 (male) 1.4 (female)
• >= 16 years: 1.7 (male) 1.4 (female)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3 x ULN (=< 135 U/L) (for the purpose of this study, the ULN for SGPT is 45 U/L)
• Serum albumin >= 2 g/dL
• Shortening fraction of >= 27% by echocardiogram OR ejection fraction of >= 50% by multi-gated acquisition (MUGA)
• Corrected QT (by Bazett's formula [QTcB]) interval < 450 msecs
• Patients must be able to swallow tablets or liquid; use of a nasogastric or gastrostomy (G) tube is also allowed
• Patients who are pregnant or breast-feeding are not eligible for this study as there is yet no available information regarding human fetal or teratogenic toxicities; negative pregnancy tests must be obtained in girls who are post-menarchal; patients of reproductive potential may not participate unless they have agreed to use an effective contraceptive method for the duration of study therapy; women of childbearing potential should be advised to use effective contraception for 4 months after the last dose of trametinib; trametinib may also potentially be secreted in milk and therefore breastfeeding women are excluded; female patients should not breastfeed during treatment with trametinib, and for 4 months following the last dose; male patients must use a condom during intercourse and agree not to father a child during therapy and for 4 months following discontinuation of trametinib to avoid unnecessary exposure of trametinib to the fetus
• Concomitant Medications
• Corticosteroids: patients requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible; if used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid
• Note: hydrocortisone used as a pre-medication to prevent transfusion related reactions is not considered a concomitant corticosteroid
• Investigational drugs: patients who are currently receiving another investigational drug are not eligible
• Anti-cancer agents: patients who are currently receiving other anti-cancer agents are not eligible (except patients receiving hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
• Anti-graft versus host disease (GVHD) or agents to prevent organ rejection post-transplant: patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial
• Cardiac medications: any medications for treatment of left ventricular systolic dysfunction
• Patients who have an uncontrolled infection are not eligible
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
• Patients with a history of hepatic sinusoid obstructive syndrome (veno-occlusive disease) within the prior 3 months are not eligible
• Patients with a history of or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
• Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension
• Patients with uncontrolled systemic disease(s) such as hypertension or diabetes mellitus are not eligible; blood pressure must be =< the 95th percentile for age, height, and gender
• Patients with a history of allergic reaction attributed to compounds of similar chemical or biologic composition to the MEK inhibitor, trametinib are not eligible
• Patients with a clinical diagnosis of Noonan syndrome are not eligible; Note: patients with Casitas B-lineage lymphoma (CBL) syndrome, also known as Noonan-like syndrome, are eligible to enroll

1. Age ≥ 18 years. 2. ECOG Performance Score of 2 or better/Karnofsky Performance score of 50-60 or better. 3. Biopsy-proven non-hematopoietic malignancy, except for germ cell cancer. Small cell lung carcinoma is eligible for this study 4. Six or more metastases on diagnostic or treatment planning imaging, which include either CT Brain (with contrast) or MR Brain (with or without contrast) imaging. 5. Largest tumor <4 cm 6. No prior SRS to the lesions which will be treated on protocol. 7. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 8. A female of child-bearing potential is any woman (regardless of sexual orientation, marital status, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). 9 Ability to understand and the willingness to sign a written informed consent. 1. Prior whole brain radiotherapy 2. Patients with leptomeningeal metastasis. (NOTE: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or equivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology, unless a parenchymal lesion can adequately explain the neurologic symptoms and/or signs. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In that patient, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.) 3. Patients with life expectancy < 4 months 4. Psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirements. 5. Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants

Key
• Male or non-pregnant, non-lactating female, age 2 to 35 years, inclusive as of the day of the Screening Visit.
• Clinical diagnosis of Lennox-Gastaut syndrome, where seizures that result in drops are not completely controlled by current antiepileptic treatments.
• Onset of seizures at 11 years of age or younger.
• Abnormal cognitive development.
• Must be receiving at least 1 concomitant AED and up to 4 concomitant anti-epileptic treatments. Key
• Etiology of seizures is a degenerative neurological disease.
• History of hemiclonic seizures in the first year of life.
• Subject only has drop seizures in clusters, where individual seizures cannot be counted reliably.
• Pulmonary arterial hypertension.
• Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
• Receiving concomitant therapy with: centrally-acting anorectic agents; monoamineoxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine.
• Taking felbamate for less than 1 year prior to screening and/or does not have stable liver function and hematology laboratory tests, and/or the dose has not been stable for at least 60 days prior to the Screening Visit.
• Currently receiving an investigational product.
• Institutionalized in a general nursing home (ie, in a facility that does not specialize in epilepsy care).
• A clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.