David Garcia-Castro (DO/PhD '23) is an aspiring physician-scientist, currently in
his third year of medical school, performing clinical rotations. He recently defended his doctoral research dissertation
at Philadelphia College of Osteopathic Medicine (PCOM). Mr. Garcia-Castro received his bachelor of science in biomedical science from Northern Arizona University in 2012 and worked in research and development in
infectious disease diagnostic assay production from 2013-2016.
Spinal and bulbar muscular atrophy (SBMA, Kennedy’s Disease) is a debilitating, neuromuscular disease that causes muscle weakness and atrophy, leading to loss of mobility. To date, no therapy exists to halt SBMA progression. Mitochondrial and metabolic dysfunction are critical pathologic features of SBMA pathology and may serve as a target for therapeutic intervention. The goals of this study were twofold: 1) to enhance mitochondrial and metabolic health in SBMA, and 2) to characterize a novel high-throughput in vivo model of SBMA to help screen potential therapeutics.
Research has always been my passion alongside medicine. I was introduced to research in 2009 when I joined my first undergraduate research lab and studied the role of the APOE gene in Alzheimer’s disease. It was a brief introduction to research but I found that I enjoyed looking at the big picture of disease pathogenesis, how finding opens up new avenues of research and how research moves the field down pathways to potential therapies. When I graduated in 2012, I continued my research work in the biotechnology field where I was able to work side-by-side with research professionals in both human and veterinary infectious disease diagnostics. I was very fortunate and thoroughly enjoyed being at the forefront of diagnostic point-of-care nucleic acid amplification technology development. When I returned to medicine, I chose this dual-degree program, which has allowed me to train in both basic science research and in clinical medicine.
Using in-vitro and in vivo models of SBMA, we targeted a major mitochondrial enzyme, which regulates mitochondrial functions and provides anti-oxidative defense. Within SBMA models, the activation and over-expression of this enzyme decreased reactive oxygen species (ROS), reduced cell death and increased muscle mass. However, the enzyme by itself did not rescue motor dysfunction. Therefore, we repurposed a previously FDA-approved drug to increase the enzyme function. With this drug, we were able to restore motor function with concurrent enzyme over-expression. Additionally, we are also developing a more high-throughput in vivo SBMA model to screen for therapeutics that could be of benefit in mammals.
This research was conducted at PCOM in Philadelphia, under the advisory of Heather Montie, PhD. The Cell and Molecular Biology PhD program, within the University of the Sciences further supported my academic PhD training. This work was supported by the CCDA, DOR, and the DO/PhD program (Giunta Family Research Scholarship to DGC) at PCOM, the Kennedy’s Disease Association (to HLM), and R03NS104607 from the NIH (to HLM).
I worked on this research project for three years during my PhD dissertation, and continue to take part in it during my clinical rotations. I was involved in troubleshooting assays, running experiments, developing research protocols, presenting research and writing my thesis and research manuscripts.
SBMA is a trinucleotide repeat neuromuscular disease that shares many aspects of pathology with other neurodegenerative diseases such as ALS, Huntington’s disease and Parkinson’s disease. Our research has identified a potential and novel therapeutic approach for SBMA, which may also be relevant to other areas of neurodegenerative and muscular atrophy research. Additionally, our work to generate a high-throughput in vivo assay will help to further support therapeutic development for SBMA.
For the past 125 years, Philadelphia College of Osteopathic Medicine (PCOM) has trained thousands of highly competent, caring physicians, health practitioners and behavioral scientists who practice a “whole person” approach to care—treating people, not just symptoms. PCOM, a private, not-for-profit accredited institution of higher education, operates three campuses (PCOM, PCOM Georgia and PCOM South Georgia) and offers doctoral degrees in clinical psychology, educational psychology, osteopathic medicine, pharmacy, physical therapy, and school psychology. The college also offers graduate degrees in applied behavior analysis, applied positive psychology, biomedical sciences, forensic medicine, medical laboratory science, mental health counseling, physician assistant studies, and school psychology. PCOM students learn the importance of health promotion, research, education and service to the community. Through its community-based Healthcare Centers, PCOM provides care to medically underserved populations. For more information, visit pcom.edu or call 215-871-6100.
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