An old disease is getting new recognition as a potential protective agent against infection and subsequent death from the Ebola virus.
Nieman-Pick Type C (NPC) is one of three lysosomal storage diseases (along with A and B) resulting from aberrations in the protein acid sphingomyelinase, coded by the NPC gene. Type C arises from sphingomyelinase changing shape and function from an enzyme to a transporter protein, resulting in accumulation of glycolipids and cholesterol in lysosomes, preventing their use in other membrane systems in the body. The disease affects ~1:150,000 people, often manifesting before the individual reaches 10 years old.
While this rare (orphan) disease is not new, research into its causes and outcomes is gaining renewed vigor after it was discovered that individuals with NPC or who are carriers of the disease either do not contract or have limited reaction to Ebola virus infection. NPC is biochemically, genetically and clinically distinct from NPA or and NPB, and therefore is the only Nieman-Pick disease that affects Ebola infection.
The NPC1 protein (the name given to the mutated sphingomyelinase) in this disorder has previously been shown to be necessary for Ebola infection in a mouse model. Other researchers have shown that mice carrying mutated genes for both copies (meaning the mouse makes NPC1 and NPC2 similar to someone with clinical NPC) were mainly protected from deadly Ebola infection, while those mice with functional NPC genes all died. As the historic Ebola outbreak plays out in West Africa, epidemiologists have noted that individuals with NPC, or carriers who have mutations in NPC1 or NPC2, usually survive the disease, compared to those with no NPC mutations.
Researchers in the US are now beginning to look at blocking NPC1 protein in healthy individuals using small molecule drug therapy. If an individual already has an NPC2 mutation, the small molecule therapy may lessen the Ebola infection but significantly increase the patient’s susceptibility to a Nieman-Pick disorder, a risk clinicians are unwilling to take.
Individuals with family members who suffer from NPC are coming forward to assist with research efforts. By coordinating blood drives and tissue donations from individuals who have NPC or are carriers, advocates are hoping to help in curing Ebola as well as advance the knowledge of NPC, especially since funding for orphan disease research is hard to come by. Commenting on the link between NPC1 and Ebola, Albert Einstein College of Medicine’s Steven Walkley said, “This shows the value of the study of rare disease.”