A scientific team at UBC and Providence Health Care genetically found that the enzyme is key in the ageing of skin, and in their study engineered mice with less wrinkled skin, despite repeated exposure to wrinkle-inducing ultraviolet (UV) light.
The findings are published in peer-reviewed journal 'Aging Cell', and raise hopes for a drug that would block the activity of Granzyme B in certain places, and thus prevent the ageing and deterioration of tissues that depend on collagen – not just skin, but blood vessels and lung passages.
According to the team, if the drug proves effective then there is potential for a cosmetic product to be developed to prevent the normal, gradual ageing of the skin, which is mostly caused by sun exposure.
viDA Therapeutics, a research-based biotechnology firm, is currently developing a Granzyme-B inhibitor based on technology licensed from UBC.
Unexpected discovery
The company was co-founded by David Granville, a professor in the Department of Pathology and Laboratory Medicine and a principal investigator in the Centre for Heart Lung Innovation of UBC and St. Paul’s Hospital, who made this unexpected discovery while investigating the role of Granzyme B in atherosclerosis and heart attacks.
He and his team wanted to see if the blood vessels of mice lacking Granzyme B were more resistant to hardening and narrowing, which is a major cause of heart attacks in humans.
In the process, they discovered that such mice retained youthful-looking skin compared to the aged skin on normal mice.
In their research, Granville’s team constructed a device to simulate sun exposure on mice in which each mouse was put in a carousel that slowly turned under UV lamps, exposing them for three to four minutes, three times a week – enough to cause redness, but not to burn.
After 20 weeks of repetitive exposure, it became clear that the skin of mice lacking Granzyme B had aged much less and their collagen was more intact, compared to the control groups.
Drug test
The company plans to test a topically applied drug within two years on people with discoid lupus erythematosus, an autoimmune disease worsened by sunlight that can lead to disfiguring facial scarring.
It is from this test that, if successful, a cosmetic product will be developed, and the drug may also be used for life-threatening conditions, such as aneurysms and chronic obstructive pulmonary disease, caused by the breakdown of collagen and other proteins that provide structure to blood vessels and lung passages.
The research is financially supported by the Canadian Institutes of Health Research (CIHR), Genome BC, and Mitacs.
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Leigh G. Parkinson, Ana Toro, Hongyan Zhao, Keddie Brown, Scott J. Tebbutt, David J. Granville. Granzyme B mediates both direct and indirect cleavage of extracellular matrix in skin after chronic low-dose ultraviolet light irradiation.Aging Cell, 2014; DOI: 10.1111/acel.12298