Discoveries led by Dr. Stephen Tapscott in Human Biology about the genetic and disease mechanisms of an inherited form of muscular dystrophy have resulted in a partnership between Fred Hutch and GlaxoSmithKline PLC to develop therapeutics to treat the disease.
The goal of the new agreement is to develop a small-molecule-based medicine to potentially reverse facioscapulohumeral muscular dystrophy, or FSHD, by inhibiting the activity of a protein that is incorrectly expressed by the DUX4 gene in people with the disease. The protein activity is what damages muscle cells and leads to progressive muscle weakness and atrophy in FSHD patients.
The genetic and disease mechanisms of FSHD were discovered by an international team of scientists led by Tapscott in a series of findings published between 2010 and early 2012. Tapscott will lead the Fred Hutch work in the GSK collaboration.
Combining breakthrough research with drug-discovery expertise
The partnership with GSK is a first of its kind for Fred Hutch, which is also the first U.S.-based institution to sign on with GSK's "Discovery Partnership with Academia" (DPAc) program. GSK launched the program last year to combine the insight and creativity of the academic world with GSK's drug-discovery expertise to turn innovative research into medicines that benefit patients.
Unlike traditional licensing agreements in which the licensee is given full control to develop a discovery, the collaboration will involve GSK and Fred Hutch scientists working together to develop, test and hopefully bring to market a clinical treatment.
"GSK has huge expertise in developing agents against protein activity, so our opportunity to work with them is fantastic," Tapscott said.
FSHD affects about one in 20,000 individuals and usually begins in late adolescence. The effects start around the facial and upper-extremity muscles and eventually progress to muscles in the lower extremity. People with more severe FSHD become wheelchair bound and their life spans are often shortened.
The team's discoveries also have implications for developing cancer immunotherapies because researchers also discovered that DUX4 regulates cancer/testis antigens. Cancer/testis antigens are encoded by genes that are normally expressed only in the human germ line but are also abnormally expressed in various tumor types, including melanoma and carcinomas of the bladder, lung and liver. This knowledge will give researchers a way to manipulate the expression of cancer/testis antigens, potentially opening the opportunity to use these antigens in a cancer vaccine.
In an era of flat federal research funding, this collaboration signals an increasing interest on the part of Fred Hutch to develop partnerships that further its lifesaving and innovative research.
"We're looking for more creative academic-industry partnerships like this one between Fred Hutch and GSK," said Dr. Ulrich Mueller, vice president of industry relations and technology transfer at Fred Hutch.
Friends of FSH Research, the National Institute of Neurological Disorders and Stroke, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases funded Tapscott's research on FSHD, which provides the scientific basis for the collaboration with GSK.
Financial terms of the Fred Hutch-GSK partnership were not disclosed.