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When UCLA’s Dr. Antoni Ribas was researching a potential therapy for melanoma, a form of skin cancer, he stumbled upon something unexpected. That unexpected discovery has now resulted in him getting a $5 million dollar award from the the governing Board of the California Institute for Regenerative Medicine (CIRM) to develop a therapy to accelerate wound healing in legs.
Venous skin ulcers are open sores on the legs that can take weeks, sometimes even years, to heal and that can cause serious complications if not treated. Around 1% of Americans have venous skin ulcers. They are usually caused by insufficient blood flow from the veins of the legs back to the heart. The resulting increased blood pressure and swelling in the legs can cause an open wound to form that is painful and difficult to heal, seriously impacting quality of life. Those most at risk of developing venous leg ulcers are older people, women and non-white populations.
There are no drugs approved by the US Food and Drug Administration (FDA) for this condition and sometimes these ulcers can lead to serious skin and bone infections and, in rare cases, even skin cancer.
In a news release from UCLA, Dr. Ribas describes how his team were testing a drug called vemurafenib on patients with melanoma. Vemurafenib falls into a category of targeted cancer drugs called BRAF inhibitors, which can shrink or slow the growth of metastatic melanoma in people whose tumors have a mutation to the BRAF gene.
“We noticed that in the first two months of taking this BRAF inhibitor, patients would begin showing a thickening or overgrowth of the skin. It was somewhat of a paradox – the drug stopped the growth of skin cancer cells with the BRAF mutation, but it stimulated the growth of healthy skin cells.”
That’s when the team realized that the drug’s skin stimulating effect could be put to good use for a whole other group of patients – those with chronic wounds.
“Aside from a few famous cases, discovering a side effect that becomes a therapeutic isn’t that common,” Ribas said. “For this reason, I had to work hard to convince somebody in my lab to follow my crazy idea and take time away from immunotherapy research and do wound healing experiments.”
Thanks to that “crazy idea” Dr. Ribas and his team are now testing a gel called LUT017 that stimulates skin stem cells to proliferate and produce more keratinocytes, a kind of cell essential for repairing skin and accelerating wound healing.
The CLIN1 grant of $5,005,126 will help them manufacture and test LUT017 in pre-clinical models and apply to the FDA for permission to study it in a clinical trial in people.
Maria T. Millan, CIRM’s President and CEO says “This program adds to CIRM’s diverse portfolio of regenerative medicine approaches to tackle chronic, debilitating that lead to downstream complications, hospitalization, and a poor quality of life.”