Disease Characteristics: NPC is a rare, inherited and fatal neurodegenerative disease. 95% of NPC cases are caused by mutations in the Npc1 gene that encodes for NPC1, a large glycoprotein which is embedded in the lysosomal membrane. Even though the exact function of NPC1 is unknown, when it is mutated or absent, both cholesterol and sphingolipids accumulate in the brain, liver, lungs, bone marrow, and spleen. Sphingolipids are known to play important roles in signal transduction and nerve-fibre insulation, and their abnormal storage leads to irreversible neurological damage. There are several disease subtypes which are categorised by the age of onset of neurological disease. The patients develop progressive disabilities such as impairment in swallowing and speech, epilepsy, cerebellar ataxia (an inability to coordinate balance, gait, extremity and eye movements), and progressive dementia. The speed of progression of symptoms depends on the age of onset, which ranges from just after birth through to late adulthood and after disease onset.
Unmet Need: There are no approved treatments for NPC in the US. Miglustat is approved in the EU, but its use only slows disease progression. There are no curative treatments currently approved for NPC and there is a significant need to improve the standard of care.
Epidemiology: The incidence of NPC is estimated to be ~1:100,000 live births worldwide.
BGT-NPC is currently completing preclinical studies, with compelling preclinical efficacy data already demonstrated.
Hughes, M.P et al. Hum Mol Genet September 2018 1;27(17):3079-3098
NB: BGT-NPC includes a novel promoter not described in the paper above
