Summary of the technology
CSIC has developed and brought to preclinical stage a novel non-invasive pharmacological treatment for Niemann Pick disease Type C (NPC) and other lysosomal storage disorders where cholesterol accumulates in the brain.
Description of the technology
Niemann Pick type C is a fatal disease caused by mutations in the cholesterol transport protein Npc1. The accumulation of cholesterol, particularly evident in lysosomes, leads to progressive neurodegeneration and to cognitive and psychiatric alterations in NPC patients. Currently, the only treatment approved for NPC is the iminosugar Miglustat, which prevents accumulation of gangliosides and delays neurological symptoms but does not cure the disease having serious side effects.
We have demonstrated that oral treatment with Efavirenz (EFV), which activates the cholesterol-degrading enzyme CYP46, prevents brain cholesterol accumulation and pathology in a mouse model for NPC (Npcnmf164mice).
We propose EFV treatment could be also suitable for many other neurological lysosomal storage disorders where brain cholesterol accumulation is a hallmark.
Main innovations and advantages
- We have shown that Npc1 is not only present in lysosomes but also in synapses where it mediates the cholesterol rearrangement necessary to put in place neurotransmitter receptors.
- Npc1 deficiency leads to cholesterol accumulation in synapses leading to morphological and functional synaptic alterations that result in memory and psychiatric issues.
- In vitro pharmacological activation of the enzyme CYP46 by EFV restores synaptic cholesterol levels and function.
- Oral treatment with EFV prevents brain cholesterol accumulation, memory and psychiatric alterations and extends life span in Npcnmf164mice.
- EFV is already used for the chronic treatment of HIV patients at doses much higher than the ones used in our study.
Desired business relationship
Current development status
Intellectual property status
Patent already applied for
Spanish National Research Council
Research & Technology Organization
Additional information (attached documents)