August 20, 2014
Drug Trial Restores Hair In Alopecia Areata Sufferers
April Flowers for redOrbit.com - Your Universe Online
Baldness, or alopecia, affects millions of people around the world. It can range from male pattern baldness (where the hair thins out gradually) to alopecia universalis (which is a total loss of all body hair). Alopecia is an equal opportunity condition, affecting both men and women across races, socio-economic statuses and age. For example, UK actor Joseph Gatt (recently seen as a Thenn wildling on HBO's Game of Thrones) developed alopecia universalis at the age of 14. Different types of alopecia have different causes.
The researchers, including Raphael Clynes, MD, PhD, and CUMC professor in the Departments of Dermatology and of Genetics and Development Angela M. Christiano, PhD, report early results from an ongoing clinical trial of the drug. These results include complete hair regrowth in several patients with moderate-to-severe alopecia areata. The report includes data from three participants, each of whom experienced total hair regrowth within five months of beginning treatment.
"We've only begun testing the drug in patients, but if the drug continues to be successful and safe, it will have a dramatic positive impact on the lives of people with this disease," said Clynes.
The hair loss from alopecia areata can be disfiguring, as it is often lost in patches on the scalp, face and body. To date, there are no known treatments that can completely restore hair. People with this condition often suffer from significant psychological stress and emotional trauma.
The mechanism for hair loss — the hair follicle being surrounded and attacked by the immune system, causing the follicle to enter a dormant state — has been known for decades. Which particular immune cell was responsible, however, remained a mystery. Four years ago, Dr. Christiano's genetic study of more than 1,000 patients with alopecia areata uncovered the first major clue — the hair follicles send a "danger" signal, not previously linked to alopecia areata, which attracts the immune cells to the follicle and provokes the attack.
The current study initially started by studying mice with alopecia areata, tracking back from the danger signal to identify the specific set of T cells that initiate the attack. Follow-up examinations of both mice and human cells revealed how the T cells attack, and suggested possible pathways to be targeted by a new class of drugs called JAK inhibitors.
The team tested two FDA-approved JAK inhibitors separately: ruxolitinib and tofacitinib. Both were able to block the immune pathways and stop the attack on hair follicles. Mice with extensive hair loss from the disease had full hair restoration within 12 weeks with both drugs. The hair persisted for several months after treatment was stopped with both drugs, as well.
The researchers collaborated with Julian Mackay-Wiggan, MD, MS, director of the Clinical Research Unit in the Department of Dermatology at CUMC and a practicing dermatologist at NewYork-Presbyterian/Columbia who treats patients with multiple types of hair loss to initiate a small open-label clinical trial of ruxolitinib, as it already had FDA approval for treatment of a blood disorder. The participants, seven women and two men, all had moderate-to-severe alopecia areata with more than a 30 percent hair loss. Within four to five months of beginning treatment, three of the participants saw complete hair restoration, along with the disappearance of the attacking T cells from the scalp.
"We still need to do more testing to establish that ruxolitinib should be used in alopecia areata, but this is exciting news for patients and their physicians," Dr. Clynes said. "This disease has been completely understudied—until now, only two small clinical trials evaluating targeted therapies in alopecia areata have been performed, largely because of the lack of mechanistic insight into it."
"The timeline of moving from genetic findings to positive results in a clinical trial in only four years is astoundingly fast and speaks to this team's ability to perform translational science of the highest caliber," said David Bickers, MD, the Carl Truman Nelson Professor of Dermatology and chair of the Department of Dermatology at CUMC and dermatologist-in-chief at NewYork-Presbyterian/Columbia. "There are few tools in the arsenal for the treatment of alopecia areata that have any demonstrated efficacy. This is a major step forward in improving the standard of care for patients suffering from this devastating disease."
Dr. Christiano, who suffers from alopecia areata herself, says that it is all too often dismissed as simply an appearance altering condition. "Nothing could be further from the truth," she said. "Patients with alopecia areata are suffering profoundly, and these findings mark a significant step forward for them. The team is fully committed to advancing new therapies for patients with a vast unmet need."
The New York Times cautions, however, that the treatment will likely not work for everyone, and not enough is known yet of side effects or safety concerns. Dr. George Cotsarelis, a dermatologist at the University of Pennsylvania, agrees that people should approach this "cure" with caution. The study participants received the drug as a twice daily pill instead of a topical cream, meaning that they were “treated systemically with a very toxic drug” known to cause liver and blood problems, infections and other negative outcomes. Dr. Cotsarelis said that if the drug could be applied topically, it would "be an amazing breakthrough."
The team plans to continue with larger clinical trials, which will include the other JAK inhibitor, tofacitinib — originally approved for rheumatoid arthritis.