Ronald G Crystal
Weill Medical College of Cornell University, NY·Medicine & Clinical Research
A single faulty gene can set off decades of damage in the lungs or the heart. Gene therapy tries to interrupt that chain by giving cells a working copy of the gene, delivered inside a harmless virus shell.
- Fields
Medicine & Clinical Research
Genetics
Physiology
- Topics
gene therapy
adeno-associated virus
alpha 1-antitrypsin deficiency
- Grants
- 3 known grants, through Apr 2028
What they work on
- Secure Investigational New Drug approval and manufacture clinical-grade AAV8hAAT(AVL), a virus vector carrying an oxidation-resistant form of alpha 1-antitrypsin, the protein that blocks lung-digesting enzymes.
- Run a phase 1 trial giving AAV8hAAT(AVL) intravenously at three dose levels to five people per dose who carry two Z copies of SERPINA1, to find the highest tolerable dose and early signs of anti-protease activity.
- Carry out dose-ranging and preliminary-efficacy trials of AAVrh.10hFXN, a virus vector delivering human frataxin, in people with Friedreich's ataxia, tracking the heart muscle changes that cause most deaths in this disease.
- Test whether basal stem cells from the small airways of people with early COPD rebuild a normal airway lining less well than cells from controls, using air-liquid interface cultures of bronchoscopy samples.
- Examine whether excess BMP4, a growth factor driving flat skin-like cells, and SPDEF, a factor driving mucus cells, explain the disordered airway lining in early COPD by activating their downstream signaling pathways.
- Correlate these cell-level measures with each SOURCE participant's clinical small airway structure and function to see whether the biology matches the earliest clinical abnormalities.
More about the research
Work here covers two such translational efforts, each moving from animal data into first-in-human safety trials, plus a third project that asks how the smallest airways of the lung begin to break down in the earliest stage of chronic lung disease.
Why it matters
Both gene therapy projects aim to replace repeated or absent treatment with one intravenous dose: lasting protection against lung destruction for people with inherited AAT deficiency, and a possible way to reverse heart muscle changes in Friedreich's ataxia, where no treatment exists and most deaths are cardiac. Because many cardiomyopathies are genetic, the approach could inform others. The COPD study could point to specific molecules worth targeting to halt airway damage before symptoms become severe.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Gene Therapy for Alpha 1-Antitrypsin Deficiency
NIH · May 2024 – Apr 2028
Ancillary SOURCE Study: Characterization of Small Airway Basal Cell Biology in Early COPD
NIH · Jun 2023 – May 2027
Phase IA/IB Study of AAVrh.10hFXN Therapy to Treat the Cardiomyopathy of Friedreich's Ataxia
NIH · Aug 2020 – Aug 2026
Closest labs
George Aslanidi
University of Minnesota, MN·Microbiology & Immunology
Test in non-human primates whether extracellular-vesicle-associated AAV vectors deliver genes efficiently to the airway lining, combining non-invasive live imaging of gene expression with post-necropsy analysis of transduced cell subpopulations.
Andrei Maiseyeu
Case Western Reserve University, OH·Pharmacology
Define which nanoparticle design parameters govern where adeno-associated virus (AAV) gene therapy vectors travel in the body and how much is taken up by heart muscle.
Alisha Gruntman
University of Massachusetts Chan Medical School, MA·Biomedical Engineering
Breed and maintain AAT-Null-PiZ ferrets, AAT-Null and AAT-Null-PiZ mice, and wild-type mice as models of alpha-1 antitrypsin deficiency (AATD) and supply them to the program's three research projects.
The school
Weill Medical College of Cornell University: 35 labs on PI Pages, $1.6B a year on research, 59 research doctorates a year.
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