# A phase 2 study of a vitamin metabolite for PKAN

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $411,268

## Abstract

Project Summary
Our broad, long-term goal is to develop rational therapeutics for the orphan disease pantothenate kinase-
associated neurodegeneration (PKAN), an inborn error of vitamin B5 metabolism that is caused by defects in
the gene that encodes PANK2, the first regulatory step in the coenzyme A biosynthetic pathway, and to do so
as cost-effectively as possible. Children and adults affected by the disease develop a severe movement
disorder and a characteristic pattern of abnormal iron accumulation in the brain. PKAN causes profound
disability and suffering, especially in children, many of whom succumb to complications of the disease in the
first decade of life. No proven disease-modifying therapy is currently available.
In this project, we will build on recent work from the laboratory demonstrating a compelling, disease-relevant
molecular and functional signature in the PKAN mouse brain that is recapitulated in both fibroblast cell cultures
and in peripheral blood from human patients. This biological signature is ameliorated in vivo and in vitro by a
product of intermediary metabolism in a dose-dependent fashion.
In this application, we propose to extend this work to the clinic, evaluating the safety, tolerability and
pharmacodynamic profile of the product in a phase 2, randomized, double-blind, placebo-controlled, dose-
ranging, parallel-group study in children and adults with PKAN. A 6-month double-blind phase will be followed
by an 18-month open-label phase. We will also explore the feasibility of applying a latent growth curve
modeling approach to longitudinal natural history data to capture a disease modifying effect, with the goal of
informing future study design. We will employ a novel approach to study conduct that is designed to reduce the
barriers to study participation inherent in rare disease clinical research, minimize risks to subjects, and lessen
the burden on families.

## Key facts

- **NIH application ID:** 10480786
- **Project number:** 5R01HD097328-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Penelope Hogarth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $411,268
- **Award type:** 5
- **Project period:** 2019-09-13 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480786

## Citation

> US National Institutes of Health, RePORTER application 10480786, A phase 2 study of a vitamin metabolite for PKAN (5R01HD097328-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10480786. Licensed CC0.

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