Helping enzyme treatments reach the brain by boosting a key receptor at the blood–brain barrier
Advancing CNS drug delivery via epigenetic modulation
Trying to raise a receptor (M6PR) on brain blood vessels so enzyme therapies can get into the brains of people with neuronopathic lysosomal storage disorders.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Cincinnati Childrens Hosp Med Ctr NIH-funded |
| Lab location | 1 site (Cincinnati, United States) |
| Project ID | NIH-11264882 on NIH RePORTER |
What this research studies
Many lysosomal storage disorders (LSDs) cause harmful buildup in the brain because replacement enzymes can't cross the blood–brain barrier. This project aims to increase the mannose-6-phosphate receptor (M6PR) on brain microvessels by targeting microRNA-143, an epigenetic regulator. Researchers will use AAV-based delivery tools, animal models, and analysis of human brain microvessel samples to see if raising M6PR improves enzyme uptake into the adult brain. The goal is to enable current enzyme replacement or gene therapies to reach and treat the CNS in people with neuronopathic LSDs.
Who could benefit from this research
Good fit: People with neuronopathic lysosomal storage disorders (nLSDs), such as Hurler syndrome, would be the primary group who could benefit from this approach.
Not a fit: Patients without central nervous system involvement or whose disease does not depend on lysosomal enzyme trafficking are unlikely to receive direct benefit.
Why it matters
Potential benefit: Could allow existing enzyme or gene therapies to get into the brain and slow or reverse neurological damage in people with neuronopathic lysosomal storage disorders.
How similar studies have performed: AAV delivery and enzyme replacement have clinical precedent and the team has preclinical data linking miR-143 to M6PR, but using epigenetic modulation to boost BBB enzyme uptake is a relatively new and experimental approach.
Where this research is happening
Cincinnati, United States
- Cincinnati Childrens Hosp Med Ctr — Cincinnati, United States (Active)
Researchers
- Principal investigator: Pan, Dao — Cincinnati Childrens Hosp Med Ctr
- Study coordinator: Pan, Dao
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.