# Gene Therapy for Xeroderma Pigmentosum - Cockayne Syndrome.

> **NIH NIH R61** · UNIVERSITY OF MINNESOTA · 2024 · $428,724

## Abstract

PROJECT SUMMARY
The goal of this project is to refine our gene therapy strategy for Xeroderma Pigmentosum-Cockayne Syndrome
(XP-CS), with the ultimate aim of improving the neurological outcomes and life expectancy for this disorder. XP-
CS is a rare, inherited DNA repair disorder that is characterized by an accelerated aging phenotype and
prominent, severe neurodegenerative complications mirroring those seen in classic Cockayne syndrome (CS),
including cognitive dysfunction, brain atrophy, neurodevelopmental delays, peripheral neuropathy, brain atrophy,
and dementia. There are several genetic subtypes of XP-CS, including one associated with pathogenic variants
in the gene ERCC5 (XPG). We have found that the Xpg-/- mouse accurately recapitulates key features of the XP-
CS phenotype, including neurological features. We have also developed a first generation adeno-associated
virus (AAV) vector capable of delivering ERCC5 that shows great promise but requires further development prior
to translation into human clinical trials. Our preliminary studies using the first generation vector in the Xpg-/-
mouse point to a clear path towards optimizing this approach, including capsid optimization, promoter
optimization, delivery optimization, dose tuning, toxicity studies, and biomarker evaluations. We expect that our
proposed studies will lead to a gene therapy strategy that overcomes many of the obstacles to translation into a
Phase 1 human clinical trial. The knowledge obtained from these studies will be generalizable, and will accelerate
the development of gene therapies for other genetic subtypes of XP-CS.

## Key facts

- **NIH application ID:** 10973290
- **Project number:** 1R61NS135019-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** CHRISTINA A. PACAK
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $428,724
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10973290

## Citation

> US National Institutes of Health, RePORTER application 10973290, Gene Therapy for Xeroderma Pigmentosum - Cockayne Syndrome. (1R61NS135019-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10973290. Licensed CC0.

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