SPX-01 Gene Therapy in Pediatric Patients With Spinal Muscular Atrophy Type 1 (RISE)

The goal of this clinical trial is to learn about the safety, and tolerability of giving an experimental gene therapy called SPX-01 to an infant with spinal muscular atrophy (SMA) type 1. SMA type 1 is a rare inherited disease that causes severe muscle weakness and can affect breathing, swallowing, and movement. SPX-01 is designed to deliver a working copy of a gene called SMN1, which does not function properly in children with SMA. The main questions this study aims to answer are: * What side effects or medical problems occur after SPX-01 is given? * What changes in the infant's movement, breathing, and overall health are observed during follow-up? One infant aged 6 months or younger with genetically confirmed SMA type 1 will take part in this study. The infant will: * Receive a single dose of SPX-01 through a vein over approximately one hour. * Attend follow-up visits over 12 months, including medical examinations, blood tests, and assessments of movement and breathing.

Inclusion Criteria: * Age 6 months or younger on the day of SPX-01 administration. * Genetically confirmed spinal muscular atrophy (SMA) type 1 due to biallelic deletion or pathogenic variants of SMN1, with one or two copies of SMN2. * Onset of symptoms from birth through 6 months of age. * Clinical findings consistent with SMA type 1, including hypotonia, delayed motor development, and poor head control. * Written informed consent from the parent(s) or legally authorized guardian. * Ability to attend scheduled study visits and comply with follow-up procedures. * Final eligibility confirmation by the principal investigator and designated eligibility committee before infusion. Exclusion Criteria: * Active viral infection, HIV infection, or positive hepatitis B or hepatitis C serology. * Invasive ventilatory support or oxygen saturation (SpO2) below 95% at screening. Noninvasive ventilation (BiPAP) for fewer than 16 hours per day may be permitted at the discretion of the treating team. * Significant concomitant medical condition considered by the principal investigator to create unacceptable additional risk. * Current or recent immunosuppressive treatment within the preceding 3 months, except for protocol-specified prophylactic corticosteroids. * Gamma-glutamyl transferase (GGT) greater than 3 times the upper limit of normal. * Total bilirubin ≥3 mg/dL or serum creatinine ≥1.8 mg/dL. * Hemoglobin below 8 g/dL or above 18 g/dL, or white blood cell count above 20,000 cells/mm³. * Anti-AAV9 antibody titer greater than 1:50. * Recent participation in another clinical trial considered to create additional risk. * Aspiration identified during swallowing assessment when alternative feeding methods are not accepted. * Presence of the SMN2 c.859G\>C variant associated with a potentially milder phenotype.