Disease Characteristics: INAD is a devastating and fatal autosomal recessive paediatric neurodegenerative disease caused by mutations in the PLA2G6 gene that affects the catalytic activity of its protein product, a calcium-independent phospholipase A2 protein located in mitochondria and axons. When PLA2G6 is defective, mitochondrial inner membrane integrity is damaged, and phospholipid accumulation in axons causes neuronal damage. Given greater disease awareness and advances in next generation sequencing technologies, INAD is increasingly diagnosed at a younger age, with the majority of affected children now diagnosed by 2 years of age. Symptoms usually begin between 6 months and 3 years of age and include a rapid decline in previously acquired skills such as walking and talking, with the subsequent evolution of seizure, axonal neuropathy and generalised spasticity leading to loss of neurodevelopmental skills and complete dependence for all daily living activities. From presentation, there is gradual loss of motor and cognitive skills, most losing ambulation by 5 years of age with the average age of death around 10 years of age.
Unmet Need: There are currently no disease-modifying treatments for INAD and affected patients derive limited clinical benefit from available medical therapies used for symptom control.
Epidemiology: The prevalence of INAD is poorly documented, it is estimated to be approximately 0.3/100,000 worldwide.
Treatment of neonatal and juvenile pla2g6-inad mice with BGT-INAD via intracerebroventricular (ICV) administration resulted in significantly extended survival, improved motor functions, as well as ameliorated neurodegeneration in multiple brain regions. Following our successful Scientific Advice meeting with the MHRA, and a Type B Pre-Investigational New Drug Application (IND) meeting with the FDA, subject to initiating a vector manufacturing campaign, we plan to initiate safety and biodistribution studies in rodents in 2024 ahead of initiating a single, Phase 1/2/3 clinical trial.
BGT-INAD has received Orphan Drug Designation by the European Commission (EC) and the U.S. Food and Drug Administration (FDA) as well as Rare Pediatric Disease Designation (RPDD) by the FDA for the treatment of INAD.
INADCure Foundation https://www.inadcure.org/
NBIA Disorders Association https://www.nbiadisorders.org/
Cure INAD UK https://www.cureinaduk.org/
