# PKAN pathogenesis and treatment

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $336,875

## Abstract

PROJECT SUMMARY/ABSTRACT
Single gene disorders provide valuable insights into mechanisms of common diseases and represent highly
tractable systems for developing rational therapeutics. PKAN (pantothenate kinase-associated
neurodegeneration) is a profoundly disabling and painful genetic disorder causing dystonia, parkinsonism,
blindness and early death in children and adults. Currently there are no disease-modifying treatments. Our
long-term goals are to elucidate pathogenesis and develop a treatment for this lethal disease.
 PKAN is an inborn error of coenzyme A (CoA) synthesis that results in neurodegeneration with brain iron
accumulation. Though brain iron accumulation is a hallmark of PKAN, the link between defective CoA
metabolism, iron dyshomeostasis, and neurodegeneration has remained unclear.
 The lack of a robust mammalian disease model of PKAN has limited research progress and still represents a
critical research resource for the field. Using a mouse knock-out of Pank2 and a new approach to separating
disease-vulnerable from disease-protected brain regions, we have discovered a set of disease-relevant brain
abnormalities. This molecular `signature' includes markers of perturbed CoA, iron, and dopamine metabolism
and oxidative phosphorylation only in the disease-vulnerable regions. We propose to investigate this powerful
model with the goals to delineate the molecular pathogenesis of PKAN, to demonstrate efficacy of a candidate
therapeutic, and to discover biomarkers that can be translated for use in human interventional trials.

## Key facts

- **NIH application ID:** 10023954
- **Project number:** 5R01NS109083-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** SUSAN J HAYFLICK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,875
- **Award type:** 5
- **Project period:** 2018-09-30 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023954

## Citation

> US National Institutes of Health, RePORTER application 10023954, PKAN pathogenesis and treatment (5R01NS109083-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10023954. Licensed CC0.

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