Back to Search Start Over

Collaborative Development of 2-Hydroxypropyl-β-Cyclodextrin for the Treatment of Niemann-Pick Type C1 Disease

Authors :
Jim Cradock
Forbes D. Porter
Elizabeth A. Ottinger
William J. Pavan
Wei Zheng
John D. Heiss
Pramod S. Terse
Steven A. Silber
Nicole M. Yanjanin
Marjo Janssen
Juan J. Marugan
Charles H. Vite
Christopher P. Austin
Steven U. Walkley
Roopa Kanakatti Shankar
Marcus E. Brewster
Lili M Portilla
Mark L. Kao
Alan Hubbs
Seameen Dehdashti
Nuria Carrillo-Carrasco
Ilona Scott
Daniel S. Ory
John C. McKew
Xin Xu
Source :
Current Topics in Medicinal Chemistry. 14:330-339
Publication Year :
2014
Publisher :
Bentham Science Publishers Ltd., 2014.

Abstract

In 2010, the National Institutes of Health (NIH) established the Therapeutics for Rare and Neglected Diseases (TRND) program within the National Center for Advancing Translational Sciences (NCATS), which was created to stimulate drug discovery and development for rare and neglected tropical diseases through a collaborative model between the NIH, academic scientists, nonprofit organizations, and pharmaceutical and biotechnology companies. This paper describes one of the first TRND programs, the development of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) for the treatment of Niemann-Pick disease type C1 (NPC1). NPC is a neurodegenerative, autosomal recessive rare disease caused by a mutation in either the NPC1 (about 95% of cases) or the NPC2 gene (about 5% of cases). These mutations affect the intracellular trafficking of cholesterol and other lipids, which leads to a progressive accumulation of unesterified cholesterol and glycosphingolipids in the CNS and visceral organs. Affected individuals typically exhibit ataxia, swallowing problems, seizures, and progressive impairment of motor and intellectual function in early childhood, and usually die in adolescence. There is no disease modifying therapy currently approved for NPC1 in the US. A collaborative drug development program has been established between TRND, public and private partners that has completed the pre-clinical development of HP-β-CD through IND filing for the current Phase I clinical trial that is underway. Here we discuss how this collaborative effort helped to overcome scientific, clinical and financial challenges facing the development of new drug treatments for rare and neglected diseases, and how it will incentivize the commercialization of HP-β-CD for the benefit of the NPC patient community.

Details

ISSN :
15680266
Volume :
14
Database :
OpenAIRE
Journal :
Current Topics in Medicinal Chemistry
Accession number :
edsair.doi...........10f69b7d2bfce3545636583c13f901fa
Full Text :
https://doi.org/10.2174/1568026613666131127160118