MSFHR-funded research identifies enzyme potentially responsible for skin blistering

2003 Scholar and 2017 Innovation to Commercialization (I2C) award recipient Dr. David Granville and his team have identified an enzyme potentially responsible for autoimmune skin blistering, and are developing an inhibitor to prevent and treat the condition.

Blisters develop when layers of skin separate and fill with fluid as a result of external damage, drug reactions, congenital conditions or an auto-immune response. In autoimmune skin blistering diseases, antibodies mistakenly attack proteins that are essential for the layers of skin to stick together, forming blisters that can cover a significant portion of the skin. This can compromise the skin’s ability to function as a barrier and temperature regulator and, depending on size and severity, can be fatal.

In research funded in part by the Michael Smith Foundation for Health Research (MSFHR) and published in Nature Scientific Reports, Granville, post-doctoral fellow Dr. Valerio Russo, and a team that includes MSFHR Research Trainees Drs. Nestor Solis and Matthew Zeglinski, identify an enzyme which is responsible for the disruption of the skin’s basement membrane and the resulting epidermal detachment and blistering.

Granville explains, “The enzyme Granzyme B is mostly absent in normal skin, but our research shows a causative relationship between the enzyme accumulating in the skin, the breakdown of adhesive and structural molecules, and skin blistering. Granzyme B acts like molecular scissors, cutting away at the proteins that anchor the skin layers together. Cleavage of these proteins not only causes the skin layers to separate and blister, but also prevents cells from healing the wound”.

In a related study, supported in part by the MSFHR I2C award, Granville’s team, including Dr. Steve Shen, Dr. Dale Cameron and the Centre for Drug Research and Development, have developed a topical Granzyme B inhibitor that promotes blister healing and reduces scarring in experimental models.

“This inhibitor represents a novel therapeutic approach for the treatment and prevention of sub-epidermal blistering and other inflammatory skin conditions,” says Granville. “With the support of an MSFHR Innovation to Commercialization award, we are working to bring this potential treatment to patients, and hope to be testing it in the clinic in the next 12 to 16 months.”

The MSFHR I2C Program is designed to help BC health researchers advance their discoveries or inventions towards use in patient populations to improve health outcomes, benefit society, and enrich the health innovation ecosystem in BC. These researchers and their research programs help grow BC’s talent pool and contribute to a strong, sustainable knowledge economy.

Dr. Granville is a professor in the Department of Pathology and Laboratory of Medicine and a principal investigator in ICORD (the International Collaboration On Repair Discoveries) at the University of British Columbia. He is also the associate director of the BC Professional Firefighters’ Burn and Wound Healing Research Laboratory and co-founder/CSO of viDA Therapeutics.