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Npc1 Mouse Models Could Shed Light On a Rare Genetic Disorder

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A rare neurodegenerative condition known as Niemann-Pick disease type C (NPC) affects about one in 150,000 people. Rare diseases like NPC are often overlooked in a clinical capacity, leaving sufferers to wade through a frustrating parade of medical mysteries. For quite some time now, researchers have used Npc1 mouse models to mimic the human Npc1 gene. Now, the results could help develop a powerful new therapy for NPC.

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What Is Niemann-Pick Disease?

First, what is Niemann-Pick disease type C, or NPC? According to the National Organization for Rare Disorders (NORD), this rare condition is a progressive genetic disorder in which the human body can’t effectively transport cholesterol and other fatty substances inside of the cells. With nowhere to go, those substances can accumulate within certain tissues, including brain tissue, damaging those areas. NPC can be fatal early in life; however, it can also take the form of a late-onset, progressive disorder with symptoms beginning in adulthood. NORD reports that, while the condition was identified more than a century ago, effective treatments are still out of reach. Fortunately, as reported in Science Daily, a new study using Npc1 mouse models could change that.

Niemann-Pick Disease and Npc1 Mouse Models

The study referenced in Science Daily was published in Nature in July of this year. The study hinges on one core cause of NPC: inherited mutations in the Npc1 gene (NPC type 1C) or the Npc2 gene (NPC type 2C). Essentially, when the Npc1 gene is mutated, cells don’t receive the cholesterol they need to support motor and intellectual function. To address this issue in mutated genes, researcher Nan Yan, Ph.D., initially led a team in researching an immune protein known as STING, short for stimulator of interferon genes. This protein aids in the body’s defense against viruses; however, the body must “dispose” of STING to complete appropriate immune responses. When the body fails to dispose of STING, it can overstimulate immune cells and cause autoimmune conditions. Yan’s team was surprised to find that STING interacts with a protein that is also produced by the Npc1 gene, marking the first time that STING has been implicated in NPC.

STING Signaling

To assess the role of STING in NPC, researchers first removed the gene for STING from mice. They also removed the Npc1 gene, a deletion that usually leads to problems in motor function. Surprisingly, the mice that lacked both the Npc1 and STING genes saw no motor decline. Ultimately, researchers realized that the protein produced by Npc1 may have a binding site for STING, allowing for proper STING disposal. This suggests that inhibiting STING could help treat certain autoimmune conditions, as well as NPC.


With this study’s findings, Yan’s team may be able to identify experimental drugs that inhibit STING. “If we can demonstrate that these compounds are effective in our animal models, we may be able to offer an effective therapy to Niemann-Pick disease patients,” Yan told Science Daily. “Niemann-Pick disease has never been considered an immune disorder. These findings put it in a whole new light.” Ultimately, understanding NPC as an autoimmune condition, as opposed to a cholesterol metabolism condition, could shed light on future treatments.


Yan’s research using Npc1 mouse models could have profound implications for individuals diagnosed with Niemann-Pick disease. This study is just another example of the powerful impacts of exploratory research, especially within the rare disease community.

Scantox is a part of Scantox, a GLP/GCP-compliant contract research organization (CRO) delivering the highest grade of Discovery, Regulatory Toxicology and CMC/Analytical services since 1977. Scantox focuses on preclinical studies related to central nervous system (CNS) diseases, rare diseases, and mental disorders. With highly predictive disease models available on site and unparalleled preclinical experience, Scantox can handle most CNS drug development needs for biopharmaceutical companies of all sizes. For more information about Scantox, visit www.scantox.com.