Collaborative development of 2-hydroxypropyl-β-Cyclodextrin for the treatment of Niemann-Pick Type C1 Disease

Elizabeth A. Ottinger, Mark L. Kao, Nuria Carrillo-Carrasco, Nicole Yanjanin, Roopa Kanakatti Shankar, Marjo Janssen, Marcus Brewster, Ilona Scott, Xin Xu, Jim Cradock, Pramod Terse, Seameen J. Dehdashti, Juan Marugan, Wei Zheng, Lili Portilla, Alan Hubbs, William J. Pavan, John Heiss, Charles H. Vite, Steven U. Walkley & 5 others Daniel S. Ory, Steven A. Silber, Forbes D. Porter, Christopher P. Austin, John C. Mckew

Research output: Contribution to journalArticle

74 Citations (Scopus)

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-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.

Original languageEnglish (US)
Pages (from-to)330-339
Number of pages10
JournalCurrent Topics in Medicinal Chemistry
Volume14
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Type C Niemann-Pick Disease
Neglected Diseases
Cyclodextrins
Rare Diseases
National Institutes of Health (U.S.)
Therapeutics
Cholesterol
Nonprofit Organizations
Pharmaceutical Preparations
Clinical Trials, Phase I
Mutation
Program Development
Drug Discovery
Ataxia
Deglutition
Biotechnology
Seizures
Lipids
Genes

Keywords

  • 2-hydroxypropyl-β-Cyclodextrin
  • Neurodegenerative rare disease
  • Niemann-Pick disease type C1
  • Translational research

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Ottinger, E. A., Kao, M. L., Carrillo-Carrasco, N., Yanjanin, N., Shankar, R. K., Janssen, M., ... Mckew, J. C. (2014). Collaborative development of 2-hydroxypropyl-β-Cyclodextrin for the treatment of Niemann-Pick Type C1 Disease. Current Topics in Medicinal Chemistry, 14(3), 330-339. https://doi.org/10.2174/1568026613666131127160118

Collaborative development of 2-hydroxypropyl-β-Cyclodextrin for the treatment of Niemann-Pick Type C1 Disease. / Ottinger, Elizabeth A.; Kao, Mark L.; Carrillo-Carrasco, Nuria; Yanjanin, Nicole; Shankar, Roopa Kanakatti; Janssen, Marjo; Brewster, Marcus; Scott, Ilona; Xu, Xin; Cradock, Jim; Terse, Pramod; Dehdashti, Seameen J.; Marugan, Juan; Zheng, Wei; Portilla, Lili; Hubbs, Alan; Pavan, William J.; Heiss, John; Vite, Charles H.; Walkley, Steven U.; Ory, Daniel S.; Silber, Steven A.; Porter, Forbes D.; Austin, Christopher P.; Mckew, John C.

In: Current Topics in Medicinal Chemistry, Vol. 14, No. 3, 2014, p. 330-339.

Research output: Contribution to journalArticle

Ottinger, EA, Kao, ML, Carrillo-Carrasco, N, Yanjanin, N, Shankar, RK, Janssen, M, Brewster, M, Scott, I, Xu, X, Cradock, J, Terse, P, Dehdashti, SJ, Marugan, J, Zheng, W, Portilla, L, Hubbs, A, Pavan, WJ, Heiss, J, Vite, CH, Walkley, SU, Ory, DS, Silber, SA, Porter, FD, Austin, CP & Mckew, JC 2014, 'Collaborative development of 2-hydroxypropyl-β-Cyclodextrin for the treatment of Niemann-Pick Type C1 Disease', Current Topics in Medicinal Chemistry, vol. 14, no. 3, pp. 330-339. https://doi.org/10.2174/1568026613666131127160118
Ottinger, Elizabeth A. ; Kao, Mark L. ; Carrillo-Carrasco, Nuria ; Yanjanin, Nicole ; Shankar, Roopa Kanakatti ; Janssen, Marjo ; Brewster, Marcus ; Scott, Ilona ; Xu, Xin ; Cradock, Jim ; Terse, Pramod ; Dehdashti, Seameen J. ; Marugan, Juan ; Zheng, Wei ; Portilla, Lili ; Hubbs, Alan ; Pavan, William J. ; Heiss, John ; Vite, Charles H. ; Walkley, Steven U. ; Ory, Daniel S. ; Silber, Steven A. ; Porter, Forbes D. ; Austin, Christopher P. ; Mckew, John C. / Collaborative development of 2-hydroxypropyl-β-Cyclodextrin for the treatment of Niemann-Pick Type C1 Disease. In: Current Topics in Medicinal Chemistry. 2014 ; Vol. 14, No. 3. pp. 330-339.
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