A Phase 1/2 Open-label Intrathecal Administration of MELPIDA to Determine Its Safety and Efficacy for Patients with Spastic Paraplegia Type 50 (SPG50) Caused by Mutation in the AP4M1 Gene.

What this Trial Is About

Researchers are evaluating MELPIDA, a gene therapy product, for treating Spastic Paraplegia Type 50 (SPG50), an ultra-rare genetic disorder causing progressive neurodegeneration, spasticity, intellectual disability, and severe motor impairment. SPG50 results from mutations in the AP4M1 gene, leading to loss of function in the adaptor protein complex 4, which affects critical protein trafficking in neuronal cells. This trial aims to assess the safety and tolerability of a single intrathecal dose of MELPIDA and explore its effects on disease burden in affected children. The study involves administering MELPIDA, which delivers a functional human AP4M1 gene via a recombinant adeno-associated virus (AAV9) through an injection into the spinal canal. This is an open-label, phase 1/2 trial focusing on a single treatment dose. Participants are children aged 4 months to 10 years with confirmed SPG50. The trial monitors safety by tracking treatment-related adverse and serious adverse events, while also evaluating efficacy through measures of spasticity using the Modified Ashworth and Tardieu scales over a 60-month period. Participants will be closely observed for up to five years after treatment to monitor any toxicities or changes in spasticity and disease progression. Assessments include clinical exams and neurological evaluations to measure motor function and spasticity levels. Safety monitoring involves tracking laboratory values and any adverse events. The long follow-up allows researchers to gather detailed information on the treatment's impact over time and the natural course of SPG50 in treated children.

Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)