A Potential New Treatment for Niemann-Pick Disease – ASHG 2016

Research presented at ASHG 2016 highlights potential new treatment for the debilitating Niemann-Pick disease.

This week, The Science Explorer has been attending some of the sessions at the American Society for Human Genetics annual meeting 2016. One of our favorite presentations was by Dr. Forbes D. Porter of the National Institutes of Health (NIH, US), who talked about a potential new treatment for the debilitating Niemann-Pick disease (NPC). He presented his team’s latest research (PgmNr 188) on Thursday the 20^th of October during session #43: Toward Therapeutic Discovery in Neurological and Neuromuscular Disorders.

NPC is a progressive, irreversible, chronically debilitating–and ultimately lethal–genetic disease. It is caused by a defect in lipid transportation within the cell, which leads to excessive accumulation of lipids in the brain, liver and spleen.

Niemann-Pick diseases are a group of genetic disorders that cause excess lipids to gather in the brain, spleen, and liver. In this talk, Dr. Forbes D. Porter, who is Clinical Director of the National Institute of Child Health and Human Development (NICHD), NIH, described how a type of Niemann-Pick disease, type C1 (NPC1) that is caused by a mutation in NPC1, is present in around 1/100,000 live births. He also explained, however, that this is likely an underestimate. The irreversible genetic disease causes neuronal cell dysfunction and ultimately, death. There are currently no Food and Drug Administation- (FDA-) approved therapies for this chronically debilitating disease.

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Dr. Porter described how in earlier preclinical studies in mice and cats, a drug candidate called VTS-270, which is a specific formulation of the cyclic sugar 2-hydroxypropyl-β-cyclodextrin (HPβCD), had been identified. It had shown promise because it increased the clearance of lipids in the brain, decreased pathology in the brain, and increased the survival rate, by delaying the progression of neurological symptoms.

During his talk, Dr. Porter discussed the results from a recent Phase 1/2a (i.e. human) clinical trial of intrathecal VTS-270. The results were based on 18 months of data and Dr. Porter explained that the trial looked at various factors including safety, tolerability, and clinical efficacy. He explained that one adverse result, which was expected, was noted in the clinical trial: ototoxicity (in the form of some mid- to high-frequency hearing loss). This hearing loss was correctable with hearing aids.

The drug candidate was able to clear certain lipid and protein biomarkers in patients. Clinical trial participants showed improvements in speech, cognition, memory and others. Dr. Porter described how the treatment significantly delayed the progression of NPC1 disease. His team has already started a multinational Phase 2b/3 trials with the new drug candidate.

Read more about some of Dr. Porter’s NPC1 research in the following paper:

Wassif, CA et al. High Incidence of Unrecognized Visceral/Neurological Late-Onset Niemann-Pick Disease, Type C1 Predicted by Analysis of Massively Parallel Sequencing Data Sets. Genetics in medicine: official journal of the American College of Medical Genetics 18.1 (2016): 41–48. PMC. Web. 21 Oct. 2016. DOI: 10.1038/gim.2015.25