Moon’s Mission: creating a replicable therapeutic framework for hereditary spastic paraplegias

Project Summary​

Patients with the genetic hereditary spastic paraplegia SPG56 develop spasticity, progressive weakness of lower limbs and neurological defects because they possess a defective CYP2U1 P450 enzyme, but no treatment exists. This consumer-driven project will leverage brain organoid models derived from hIPSC lines from patients with the genetic hereditary spastic paraplegia SPG56 to test the safety and efficacy of viral gene delivery therapy and benchmark this novel platform against classical mouse model testing.

The mission leverages hiPSC lines from the patients and their parents that were established with support of the patient advocacy organisation "GC4K". In this project we combine our team's track record in generating and analysing cortical and spinal cord organoids, our extensive expertise in the design, delivery and optimisation of adenoviral gene therapy applications for neurological diseases, our world class expertise in P450 enzymology, and formidable clinical team involved in the diagnosis and treatment of hereditary spastic paraplegia patients (including this SPG56 cohort) to establish the world's first gene therapy for SPG56 patients.

This program of work will establish the world's first actionable data on the feasibility of gene therapy options for patients with currently untreatable SPG56 hereditary spastic paraplegia (information that is needed to proceed to clinical trials) and will exemplify a replicable framework for the >70 other genetic hereditary spastic paraplegias that also need novel therapeutics. As such this mission will build new critical capacity for gene therapy, incentivizes regulatory change by for the first time using human brain models to test gene therapy, and has the potential to deliver improved health outcomes for hereditary spastic paraplegia patients with SPG56.