# Intravenous delivery of 2-hydroxypropyl-Beta-cyclodextrin for treatment of Niemann-Pick C disease

> **NIH NIH U01** · WASHINGTON UNIVERSITY · 2022 · $519,342

## Abstract

ABSTRACT
Niemann-Pick type C1 (NPC1) disease is a rare, neurodegenerative cholesterol storage disorder. Affected
individuals typically present in early childhood with ataxia and progressive impairment of motor and intellectual
function, and usually die in adolescence, though increasingly NPC disease is being recognized among the
adult population with cognitive defects. There are currently no FDA-approved therapies for this progressively
fatal neurodegenerative disorder. In preclinical studies, treatment with 2-hydroxypropyl-β-cyclodextrin (HP-β-
CD) has been shown to reduce both cholesterol and sphingolipid storage and prolong survival, and has been
advanced to clinical trials. A Phase 1/2a trial of intrathecal (IT) HP-β-CD was initiated at the NIH Clinical
Center in January 2013, and in collaboration with Vtesse, Inc., an international, multisite Phase 2b/3 trial of IT
VTS-270 (a specific formulation of HP-β-CD) was launched in September 2015. While IT delivery of VTS-270
in the clinical trials directly addresses the neurodegenerative component of NPC disease, visceral
manifestations of the disease are left untreated. In infantile and juvenile forms of NPC disease, patients
typically present with neonatal cholestasis or hepatosplenomegaly, and in severe cases may progress to liver
failure. In older NPC patients, 2-3-fold chronic elevation of serum transaminases (ALT/AST) and liver
inflammation are common. We hypothesize that reduction of hepatic cholesterol storage through intravenous
(IV) delivery of VTS-270 will be effective in reducing liver inflammation in NPC1 patients. We will test this
hypothesis by (1) performing a Phase 1/2a, open-label, single-center, randomized study of IV VTS-270 in
human NPC1 subjects (≥ 3 years old) at the NIH Clinical Center, and (2) conducting a Phase 1/2a, open-label,
multi-center, dose escalation study of IV VTS-270 to establish safety and potential clinical efficacy in treating
cholestatic liver disease in infants (< 3 years old) with NPC1 at Johns Hopkins and Washington University
sites. Our primary objective is to determine the safety and tolerability of intravenous VTS-270 in NPC1 disease.
Secondary objectives will be to evaluate the efficacy of VTS-270 to reduce plasma cholestane-3β,5α,6β-triol,
an NPC1-specific pharmacodynamic biomarker, and to normalize liver function tests, as well as the
examination of exploratory lipid and protein biomarkers. Clinical efficacy will be evaluated by assessment of
liver function tests, determination of liver size, and changes in liver histopathology. Biochemical efficacy will be
assessed by measurement of plasma cholestane-3β,5α,6β-triol and other biomarkers. We anticipate that
treatment with IV VTS-270 monthly will reduce liver inflammation and restore normal hepatic function. In both
NPC groups, long-term treatment with IV VTS-270 would be expected to prevent liver fibrosis and lower risk of
hepatocellular carcinoma.

## Key facts

- **NIH application ID:** 10014634
- **Project number:** 5U01HD090845-04
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** PATRICIA I DICKSON
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $519,342
- **Award type:** 5
- **Project period:** 2017-07-10 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10014634

## Citation

> US National Institutes of Health, RePORTER application 10014634, Intravenous delivery of 2-hydroxypropyl-Beta-cyclodextrin for treatment of Niemann-Pick C disease (5U01HD090845-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10014634. Licensed CC0.

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