Martin K. (Casey) Childers, D.O., Ph.D. is a professor in the Department of Rehabilitation Medicine and Investigator at the Institute for Stem Cell & Regenerative Medicine, University of Washington(ISCRM). He is a graduate of Seattle Pacific University (B.A., Music Performance), Western University (D.O., Medicine, Osteopathic) and The University of Missouri (Ph.D., Physiology & Pharmacology; residency, Rehabilitation Medicine).
The Childers’ laboratory works in two areas of investigation.
In collaboration with the French biotechnology institute, Genéthon (Ana Buj-Bello), work on gene replacement therapy for patients with a rare and deadly muscle disease began with case report in 2008, where a 5-month-old Labrador retriever was reported in a Canadian veterinary medical journal. The dog presented with severe muscle weakness. Further analysis indicated that the dog was affected with a rare disease, termed “Labrador myopathy”. Through the tireless efforts of the mother of a child affected with a rare – and analogous- disease, termed myotubular myopathy, the Childers research group was able to acquire a first-degree relative, a dog named “Nibs”, a Labrador retriever coming from a line of dogs with a history suspicious for the rare disease. It was later discovered that Nibs harbored a canine gene mutation, the same gene known to cause myotubular myopathy in patients. Through patient donations, a canine research colony was started. Dogs in this colony later provided the “proof-of-principle” that gene replacement worked to “cure” affected dogs, but the treatment worked far better than previously thought possible. Based on this unexpected and groundbreaking discovery, the biotech company, Audentes Therapeutics, was founded in 2012 dedicated to bring gene therapy to the first human myotubular myopathy clinical trial.
In 2012, a graduate student in the Childers lab discovered that cells found in the urine of a patient with Duchenne muscular dystrophy (DMD) could be collected, expanded in a petri dish, an “reprogrammed” to form beating human heart cells. This discovery was important, because for DMD patients, the ultimate cause of death is heart failure. The student’s discovery led the group to develop tests that could be adapted for drug discovery. The first experiment at the High Throughput Core facility at ISCRM, was recently completed using this “disease in a dish” approach. Millions of beating heart cells reprogrammed from the urine of a patient with Duchenne muscular dystrophy were grown in culture, and later screened against 2000 compounds and FDA approved drugs. This “disease-in-a-dish” screening approach discovered ~40 compounds and drugs that enhanced the survival of DMD heart cells. Ongoing work will identify the most promising new compounds for further development.
Here you can find the most recent article on genetherapy.
In 2016 Casey Childers gave a talk together with Ana Buj-Bello at the family conference #TogetherEvenStronger on the topic:
How is Gene therapy working? What have we learnt from the work with dogs? What happens to bring this to a human clinical trial?
We have previously shown that gene therapy is efficacious in both mice and dogs affected by myotubular myopathy. During our presentation, we will provide an overview on how gene therapy works.
David L. Mack, Karine Poulard, Melissa A. Goddard, Virginie Latournerie, Jessica M. Snyder, Robert W. Grange, Matthew R. Elverman, Jérôme Denard, Philippe Veron, Laurine Buscara, Christine Le Bec, Jean-Yves Hogrel, Annie G. Brezovec, Hui Meng, Lin Yang, Fujun Liu, Michael O’Callaghan, Nikhil Gopal, Valerie E. Kelly, Barbara K. Smith, Jennifer L. Strande, Fulvio Mavilio, Alan H. Beggs, Federico Mingozzi, Michael W. Lawlor, Ana Buj-Bello, Martin K. Childers (2017)
Systemic AAV8-mediated gene therapy drives whole-body correction of myotubular myopathy in dogs, Molecular Therapy [in press, DOI: http://dx.doi.org/10.1016/j.ymthe.2017.02.004]
Lawlor MW, Armstrong D, Viola MG, Widrick JJ, Meng H, Grange RW, Childers MK, Hsu CP, O’Callaghan M, Pierson CR, Buj-Bello A, Beggs AH. (2013), Enzyme replacement therapy rescues weakness and improves muscle pathology in mice with x-linked myotubular myopathy. Hum Mol Genet. 2013 Apr 15;22(8):1525-38.
This publications explains successful enzyme replacement in mice.