gene transfer clinical trial for mucopolysaccharidosis (mps) iiib

Conditions: Mucopolysaccharidosis Type 3 B

Summary: open-label, dose-escalation clinical trial of raav9.cmv.hnaglu injected intravenously through a peripheral limb vein

adeno-associated virus serotype 9 carrying the human naglu gene under the control of a cmv enhancer/promoter (raav9.cmv.hnaglu) will be delivered one-time through a venous catheter inserted into a peripheral limb vein. a tapering course of prophylactic enteral prednisone or prednisolone will be administered for a period of at least two months.

Eligibility criteria:
inclusion criteria: * confirmed diagnosis of mpsiiib by both of the following two methods: * no detectable or significantly reduced naglu enzyme activity by plasma. * genomic dna analysis demonstrating homozygous or compound heterozygous mutations in the naglu gene * age: from birth to 2 years or children older than 2 years with a minimum cognitive development quotient (dq) of 60 or above (calculated by bayley scales of infant and toddler development - third edition) exclusion criteria: * inability to participate in the clinical evaluation as determined by principal investigator * identification of two nonsense or null variants on genetic testing of the naglu gene * has evidence of an attenuated phenotype of mps iiib * presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics * active viral infection based on clinical observations as infections by adenoviruses, epstein-barr virus, cytomegalovirus, respiratory syncytial virus * concomitant illness or requirement for chronic drug treatment that in the opinion of the pi creates unnecessary risks for gene transfer , or precludes the child from participating in the protocol assessments and follow up as autoimmune diseases requiring immunosuppression, such as juvenile rheumatoid arthritis or idiopathic thrombocytopenia purpura * subjects with total anti-aav9 antibody titers ≥ 1:100 as determined by elisa binding immunoassay * subjects with a positive response for the elispot for t-cell responses to aav9 * serology consistent with exposure to hiv, or serology consistent with active hepatitis b or c infection * bleeding disorder or any other medical condition or circumstance in which a lumbar puncture (for collection of csf) is contraindicated according to local institutional policy * visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing * uncontrolled seizure disorder * any item (braces, etc.) which would exclude the subject from being able to undergo mri according to local institutional policy * any other situation that precludes the subject from undergoing procedures required in this study * subjects with cardiomyopathy or significant congenital heart abnormalities * the presence of significant non-mps ilib related cns impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study * abnormal laboratory values grade 2 or higher as defined in ctcae v4.0 for ggt, total bilirubin, creatinine, hemoglobin, wbc count, platelet count, pt and aptt * female participant who is pregnant or demonstrates a positive urine or serum result at screening assessment (if applicable). * any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone) * previous treatment by haematopoietic stem cell transplantation * previous participation in a gene/cell therapy or ert clinical trial

Keywords: mps iiib sanfilippo syndrome b