# Innovative systemic gene therapy for treating Parkinson's disease

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $509,534

## Abstract

PROJECT SUMMARY
Parkinson's disease (PD) is an increasingly prevalent neurological disorder that currently affects about one
million people in the United States and 10 million worldwide. Despite recent innovations, most advanced
pharmacological and surgical therapeutic regimens remain moderately palliative and symptomatic at best.
Gene therapy has emerged as an alternative promising means to halt the disease progression or potentially
cure the disease. However, clinical trials of PD gene therapy up to this moment have failed to establish a
meaningful therapeutic benefit due to an inability to achieve widespread and efficient gene transfer to the
disease areas within the brain. The significance of this problem is highlighted by an ongoing human trial,
wherein improving the penetration and efficiency of transfection is a primary goal. Further, lacking a reliable
method to deploy gene therapy from the bloodstream to the brain tissue, all clinical studies to date have
employed highly invasive administration modalities involving direct injection of the therapy into the brain. This
reality has precluded the inclusion in clinical trials of early stage PD patients who are more likely to respond to
the therapy. Thus, new methods to overcome long-standing barriers to systemic gene delivery throughout the
PD-associated brain regions, including the tightly sealed blood-brain barrier (BBB) and the dense network of
brain extracellular matrix (ECM), are sorely needed. To this end, we propose innovative delivery approaches
exploiting: (i) clinically operable MR image-guided focused ultrasound (FUS) to transiently open the BBB for
the penetration of gene therapy into the brain tissues and cells in a targeted manner, (ii) DNA-loaded
nanoparticles possessing a unique capability to efficiently spread through the brain ECM to reach and transfect
cells in the disease areas within the brain (i.e. DNA-loaded brain-penetrating nanoparticle or DNA-BPN), and
(iii) FUS-mediated pre-conditioning that further enhances the dispersion of DNA-BPN within the brain by
temporarily reducing ECM resistance. We recently showed in our pilot study that FUS-mediated, targeted BBB
penetration of, and subsequent widespread gene transfer by, our first-generation DNA-BPN resulted in
therapeutically relevant gene therapy of a conventional neurotoxin-based preclinical model of PD. As a next
step towards clinical translation, we here propose to further refine and evaluate our combined delivery strategy
in highly sophisticated and clinically-relevant preclinical models of familial and sporadic PD that closely mimic
pathophysiological features and disease phenotypes observed in human PD. If successful, the proposed
approach could be rapidly translated to the clinic using a gene-encoding a neurotrophic factor (that is currently
under clinical investigation and will be studied here) while additional preclinical studies could be followed to test
the effectiveness of novel genetic targets in these ad...

## Key facts

- **NIH application ID:** 10164880
- **Project number:** 5R01NS111102-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Richard J. Price
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $509,534
- **Award type:** 5
- **Project period:** 2019-05-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164880

## Citation

> US National Institutes of Health, RePORTER application 10164880, Innovative systemic gene therapy for treating Parkinson's disease (5R01NS111102-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10164880. Licensed CC0.

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