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

MELPIDA is proposed for the treatment of subjects with SPG50 and targets neuronal cells to deliver a fully functional human AP4M1 cDNA copy via intrathecal injection to counter the associated neuronal loss. Outcomes will evaluate the safety and tolerability of a single dose of MELPIDA, which will be measured by the treatment-associated adverse events (AEs) and serious adverse events (SAEs). Secondarily, the trial will explore efficacy in terms of disease burden assessments.

Inclusion Criteria: 1. Age 4 months-10 years old 2. Confirmed diagnosis of SPG50 disease by: 1. Genomic DNA mutation analysis demonstrating homozygous or compound heterozygous, confirmed pathogenic variants in the AP4M1 gene 2. Clinical history or examination features consistent with SPG50 and that include neurologic dysfunction 3. Parent/legal guardian willing to provide written informed consent for their child prior to participation in the study 4. Subject able to comply with all protocol requirements and procedures 5. Ability to stand for more than 5 seconds OR 6. Ability to take 5 steps independently or with a walker OR 7. Modified Ashworth Scale score 2 or below (Ankles). Exclusion Criteria: 1. Inability to participate in study procedures (as determined by the site investigator) 2. Presence of a concomitant medical condition that precludes lumbar puncture (LP) or use of anesthetics 3. History of bleeding disorder or any other medical condition or circumstance in which lumbar puncture is contraindicated according to local institutional policy 4. Inability to be safely sedated in the opinion of the clinical anesthesiologist 5. Active infection, at the time of dosing, based on clinical observations 6. Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer 7. Inability of the patient to undergo MRI according to local institutional policy 8. Inability of the patient to undergo any other procedure required in this study 9. The presence of significant non-SPG50 related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study 10. Have received an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study. 11. Enrollment and participation in another interventional clinical trial 12. Contraindication to MELPIDA or any of its ingredients 13. Contraindication to any of the immune suppression medications used in this study 14. Clinically significant abnormal laboratory values (GGT, ALT, and AST, or total bilirubin \> 3 × ULN, creatinine ≥ 1.5 mg/dL, hemoglobin \[Hgb\] \< 6 or \> 20 g/dL; white blood cell \[WBC\] \> 20,000 per cmm) prior to gene replacement therapy.