• Spinal Muscular Atrophy Gene Therapy Clinical Trial

    Gene Therapy

    Phone: 617-632-5064  

    Study of Inthrathecal Administration of AVXS-101 for Spinal Muscular Atrophy

    Spinal muscular atrophy (SMA) is a rare genetic condition in which muscles throughout the body are weakened because cells in the spinal cord and brainstem do not work properly. Typically, SMN1 genes provide instructions for producing SMN proteins, which are needed for motor neurons (nerve cells that control motor function) to survive. SMA is caused by a mutation in the SMN1 gene, which leads to a deficiency of survival motor neuron (SMN) proteins.

    This Phase I study aims to evaluate the safety and tolerability of AVXS-101, a form of gene therapy that delivers a working copy of the SMN1 gene to motor neurons in SMA patients.

    Patients participating in this study must have three copies of the SMN2 gene. The SMN2 gene is nearly identical to the SMN1 gene with the major difference being a single nucleotide that leads to unstable proteins that serve no biological function.

    Inclusion Criteria:

    • Patients up to 60 months of age at the time of dosing
    • Patients must 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
    • Onset of clinical signs and symptoms consistent with spinal muscular atrophy (SMA) before 12 months of age

    Exclusion Criteria:

    • Current or historical ability to stand or walk independently
    • Contraindications for spinal tap procedure or administration of intrathecal therapy (e.g., spina bifida, meningitis, impairment, or clotting abnormalities, or obstructive spinal hardware preventing effective access to cerebrospinal fluid (CSF) space) or presence of an implanted shunt for the drainage of CSF or an implanted central venous (CNS) catheter
    • Severe contractures as determined by physical therapist(s) at the patient screening that interfere with either the ability to attain/demonstrate functional measures (e.g., standing, walking) or interferes with the ability to receive intrathecal (IT) dosing
    • Severe scoliosis (defined as less than or equal to a 50° curvature of spine) evident on X-ray examination
    • Previous, planned or expected scoliosis repair surgery/procedure within 1 year of the dose administration
    • Use of invasive ventilatory support (tracheotomy with positive pressure) or pulse oximetry at less than 95% saturation while the patient is awake
    • Use or requirement of non-invasive ventilatory support for 12 or more hours daily over the two 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 third percentile based on World Health Organization (WHO) Child Growth Standards

    Learn More: