Niemann-Pick Type C disease
Lysosomal storage diseases (LSDs) comprise a group of approximately 60 unique orphan diseases that are caused by genetic defects leading to total deﬁciency or reduced activity of speciﬁc enzymes within the so called lysosomal compartment of the cell. As a result, compounds that are normally broken down by these enzymes, accumulate and cause progressive damage in connective tissue, skeletal structure, various organs, and, in some cases, the central nervous system. The clinical manifestations of the diﬀerent LSDs are very diverse and depend a.o. on the type of enzyme defect and age of onset. Symptoms range from mild to severe multi‐organ failure and several infantile and juvenile forms of the LSD’s lead to premature death. Although each LSD is individually relatively rare, as a group they have a rather high incidence of about 1 per 7,000 to 8,000 live births.
Niemann-Pick Type C (NPC) is lysosomal storage disease characterized by a cellular accumulation of cholesterol due to a genetic defect in speciﬁc lysosomal cholesterol transporting proteins. Although in NPC cholesterol accumulation is most pronounced in visceral organs (liver, spleen), the detrimental eﬀects of the disease on the brain are most prominent in the mostly very young patients.
Recent developments and scientific findings strongly suggest a role for cyclodextrins in modifying some pathological processes in Niemann-Pick type C disease. Okklo is developing novel proprietary cyclodextrins with better pharmacodynamic and pharmacokinetic properties for the treatment of NPC.