Heather L Montie
Philadelphia College of Osteopathic Medicine, PA·Neuroscience
Spinal and bulbar muscular atrophy (SBMA), also called Kennedy's disease, is an inherited disorder that slowly weakens muscles in men. It is caused by a repeated stretch of DNA in the androgen receptor (AR) gene.
- Fields
Neuroscience
Pharmacology
Physiology
- Topics
spinal and bulbar muscular atrophy
Kennedy's disease
androgen receptor
- Grants
- 2 known grants, through Dec 2029
What they work on
- Test whether excess CD38 activity, which breaks down the energy molecule NAD+, drives NAD+ depletion and motor decline in AR100Q and AR113Q knock-in mouse models of SBMA.
- Evaluate more clinically relevant CD38 inhibitors for their ability to restore NAD+, glycolysis, TCA cycle activity and motor function in SBMA mice.
- Measure inflammation in SBMA muscle and determine how much CD38-expressing immune cells, compared with muscle fibers, contribute to NAD+ loss.
- Profile metabolic changes in skeletal muscle grown from SBMA patient iPSCs, comparing them with CRISPR-corrected control cells from the same patients.
- Generate a Cre-Lox inducible zebrafish line expressing human polyglutamine-expanded AR, and test whether larvae develop motor dysfunction suitable for rapid drug and genetic screens.
More about the research
That repeat adds an abnormally long chain of the amino acid glutamine to the AR protein. There is no treatment that changes the course of the disease. Both projects look for ways to find therapies: one targets a specific energy-draining enzyme, and the other builds a fast, inexpensive animal model for screening drugs.
Why it matters
Men with SBMA currently have no disease-modifying therapy. CD38 inhibitors are already in clinical development, so showing that blocking CD38 restores muscle energy could provide a rationale for future trials in SBMA patients. A rapid zebrafish screening model could speed the search for treatments. Targets found this way may also be relevant to other polyglutamine and neuromuscular diseases.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Charlotte Sumner
Johns Hopkins University, MD·Neuroscience
Dissect how levels of SMN protein, which declines sharply around birth in SMA, are regulated during development and during treatment with SMN-inducing drugs, using patient data, mice and iPSC-derived motor neurons.
Wanling Xuan
University of South Florida, FL·Physiology
Test whether muscle progenitor cells made from human iPSCs with givinostat, a histone deacetylase–blocking drug, are effective and safe for regenerating aged muscle in an animal model of sarcopenia.
Masayuki Yazawa
Icahn School of Medicine at Mount Sinai, NY·Pharmacology
Design, synthesize and characterize new small-molecule Sigma 1 receptor agonists that relieve Timothy syndrome heart cell defects, testing them in human iPSC-derived heart muscle cells and rodent models.
The school
Philadelphia College of Osteopathic Medicine: 1 labs on PI Pages, $8M a year on research.
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