This is a clinical research trial targeting the Type 1 Spinal Muscular Atrophy (SMA) patient population.
- Center for Gene Therapy
- The Research Institute at Nationwide Children’s Hospital
- 700 Children’s Drive
- Columbus, OH 43205
Principal Investigator: Jerry R Mendell, M.D.
The study will evaluate safety and efficacy of gene transfer in Spinal Muscular Atrophy Type 1 (SMA1) patients. SMA is caused by low levels of the survival motor neuron (SMN) protein, and affects all muscles in the body. There is no other effective treatment for SMA and current drug therapy has been unsuccessful in stabilizing or reversing this disease. Only supportive care is currently possible.
The gene transfer trial will deliver SMN gene intravenously (i.v.) using the adeno-associated virus serotype 9 (AAV9). This dose escalation study involves three cohorts. The first cohort will receive a low dose, the second cohort will receive an intermediate dose, and the third cohort will receive a maximal dose.
The primary objective of this study is the assessment of the safety of scAAV9.CB.SMN delivered intravenously to SMA type 1 patients. Following gene transfer i.v. infusion, participants will be carefully monitored for any side effects at the outpatient follow-up visits weekly for 3 weeks followed by monthly visits over two years of active study period. Safety endpoints will be assessed by changes in hematology, serum chemistry, urinalysis, immunologic response to rAAV9 and SMN, and reported history and observations of symptoms. The time from birth to study pre-defined use of respiratory assistance devices or death will be used as a secondary outcome measure of efficacy. Exploratory outcome measures include nerve conduction and muscle assessment studies. The active phase of this study will last for two-years post-infusion, following which, participants will be asked to transfer into a monitoring program where medical progress will continue to be collected from annual standard care medical exams for the next 15 years.
 Eligibility
| Ages Eligible for Study: | up to 9 Months |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Nine months of age and younger at day of vector infusion with Type 1 SMA as defined by the following features:
- Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN2.
- Onset of disease at birth up to 6 months of age.
- Hypotonia by clinical evaluation with delay in motor skills, poor head control, round shoulder posture and hypermobility of joints.
Exclusion Criteria:
- Active viral infection (includes HIV or serology positive for hepatitis B or C)
- Use of invasive ventilatory support (tracheotomy with positive pressure)* or pulse oximetry <95% saturation.
- Patients may be put on non-invasive ventilator support (BiPAP) for less than 16 hours a day at the discretion of their physician or research staff.
- Concomitant illness that in the opinion of the PI creates unnecessary risks for gene transfer
- Concomitant use of any of the following drugs: drugs for treatment of myopathy or neuropathy, agents used to treat diabetes mellitus, or ongoing immunosuppressive therapy or immunosuppressive therapy within 3 months of starting the trial (e.g. corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab)
- Patients with Anti-AAV9 antibody titers >1:50 as determined by ELISA binding immunoassay.
- Abnormal laboratory values considered clinically significant (GGT > 3XULN, bilirubin ≥ 3.0 mg/dL , creatinine ≥ 1.8 mg/dL, Hgb < 8 or > 18 g/Dl; WBC > 20,000 per cmm)
- Participation in a recent SMA treatment clinical trial that in the opinion of the PI creates unnecessary risks for gene transfer.
- Family does not want to disclose patient’s study participation with primary care physician and other medical providers.
- Patient with signs of aspiration based on a swallowing test and unwilling to use an alternative method to oral feeding.
