Pepper Compound Could Aid Millions With Vitiligo

Vitiligo, which afflicts an estimated 100 million people worldwide, is characterized by the loss of pigment in affected areas of skin. It is the disease pop star Michael Jackson has publicly disclosed that he has. It is neither life-threatening nor contagious. But the sometimes unsightly white patches it causes produce emotional distress for many and often lead to social ostracism because of a widespread misperception that the condition is infectious.

An estimated 1 percent to 2 percent of the world’s population suffers from the malady. Current treatments, which rely on immunosuppression or ultraviolet radiation to stimulate repigmentation, are only partially effective, often producing a mottled appearance. Excessive ultraviolet (UV) radiation also poses the risk of skin cancer.

“Based on the animal studies we have done, these compounds, if proved safe in humans, promise far superior results in the treatment of vitiligo than current approaches,” said Amala Soumyanath, Ph.D., an associate professor of neurology, OHSU School of Medicine. “Vitiligo is a highly visible disease that can greatly affect patients psychologically and emotionally, even driving some to consider suicide. Any breakthrough in treating it would benefit a huge number of people around the world.”

Soumyanath and her collaborators reported on the effects of their compounds in animals in a paper just published in the British Journal of Dermatology. But development of the concept dates back more than a decade. Soumyanath discovered – in research on vitiligo that she initiated at King’s College London – that piperine, the alkaloid in black pepper responsible for its pungency, stimulated the proliferation of melanocytes in cell cultures. Melanocytes are the cells that produce pigmentation in the skin. The researchers then designed and tested many synthetic piperine analogs and identified a number that produced the same result.

The group subsequently found that piperine and two of its analogs – tetrahydropiperine (THP) and a cyclohexyl derivative (RCHP) produced light, even pigmentation when applied to the skin of a poorly pigmented mouse model. When combined with UV radiation, the skin grew significantly darker and showed none of the patchiness caused by UV treatment alone. Moreover, skin pre-treated with a piperine compound required fewer UV exposures, thus lowering the cancer risk, and it took longer for the pigmentation to fade again than when UV alone was used.

Since coming to OHSU in 2002, Soumyanath has established new collaborations with scientific and clinical researchers to continue work on this project. “Dr. Soumyanath’s recent discoveries open up completely new and exciting treatment possibilities for those individuals affected by vitiligo,” said Andrew Blauvelt, M.D., professor of dermatology at OHSU and one of Soumyanath’s recent collaborators. “There is a huge unmet need for this disease because we have very few treatments to offer patients right now,” he noted. 

OHSU acquired the patents to Soumyanath’s piperine compounds from King’s College London and BTG International Ltd. in 2006 and succeeded in finding a commercial partner, AdPharma, to advance the compounds through pharmaceutical development. Soumyanath has a financial interest in AdPharma. This potential conflict has been disclosed to the OHSU Conflict of Interest in Research committee for management.

AdPharma, a diverse pharmaceutical company headquartered in Arlington Heights, Ill., licenses promising compounds from scientists, universities and biotech companies and advances them through the clinical testing stage. “Our key strength is being able to identify, through our computer models and past experience, promising drugs which we can then drive through our strong development structure,” said Anil Sunkara, the company’s chief executive officer.

The next step before clinical trials can be undertaken, said Soumyanath, is to determine in animal models whether the repigmentation effects of piperine compounds is associated in any way with melanoma or other skin cancers. “From our mouse studies so far, it doesn’t appear that is the case,” she said, “and we are hopeful that more detailed research will bear this out. OHSU has ideal facilities and expertise for further preclinical and clinical studies, and we are excited to have the support of AdPharma as we move toward testing these compounds in human vitiligo.”