New research by the Providence Health Care Research Institute (PHCRI) tackles a major problem plaguing long-term care facilities and hospitals.
The study, published in the Nature Publication Group journal Cell Death and Differentiation, gives hope to those with chronic non-healing wounds, a problem affecting as many as 20-25 per cent of patients in long-term care facilities.
As we age, the skin becomes thinner and weaker reducing its capacity to heal. The elderly and people affected with immobility, diabetes and/or obesity are highly susceptible to developing skin wounds that do not close and heal properly.
The article entitled “Granzyme B degrades extracellular matrix and contributes to delayed wound closure in apolipoprotein E knockout mice” shows that inhibition of Granzyme B improves the healing of chronic, non-healing wounds. This is the first study to show that inhibiting this protein-degrading enzyme, that builds up with age and chronic inflammation, can restore normal wound healing. The study was funded in part through a Canadian Institutes for Health Research Industry Partnership grant.
The study was led by Dr. Paul Hiebert, a former PhD candidate in the laboratory of Dr. David Granville, Principal Investigator at the Centre for Heart and Lung Innovation at St. Paul’s Hospital, Professor in the Department of Pathology and Laboratory Medicine at the University of British Columbia and Founder and CSO, viDA Therapeutics, Inc.
“It is becoming clear that Granzyme B does a lot more than we once thought,” says Dr. Hiebert. “It is capable of chewing up the structural proteins in skin that are crucial for proper healing, similar to hungry termites eating the wooden frame of a house while it’s being built.”
“Chronic ulcers are common in hospitals and long-term care facilities, resulting in enormous costs to the health care system,” noted Dr. Granville. “The present study provides important proof-of-concept data to support the notion that drugs targeting Granzyme B could be used as a therapy to improve the lives of so many that are affected by this inability to heal normally.”
Chronic, non-healing wounds affect millions of people across North America resulting in $6 billion in estimated costs to the health-care system in the US alone. The degree of morbidity and mortality associated with these wounds is similar to that of many types of cancer. Studies are currently under way at viDA Therapeutics, a spin-off company from the University of British Columbia, to further validate Granzyme B as a therapeutic target and to develop and assess new compounds for therapeutic efficacy. However, at present, the inhibitors are still being developed and not available for clinical applications.