Old drug restores hair in alopecia areata patients
20 August 2014
Researchers at Columbia University Medical Center (CUMC) have
tested a drug that has eliminated the immune cells attacking hair
follicles and restored hair growth in a small number of patients.
The researchers have reported in Nature Medicine the
initial results from an ongoing clinical trial of the drug, which
has produced complete hair regrowth in several patients with
moderate-to-severe alopecia areata. Data from three participants
appear in the current paper; each patient experienced total hair
regrowth within five months of the start of 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
Raphael Clynes, MD, PhD, who led the research, along with Angela M.
Christiano, PhD, professor in the Departments of Dermatology and of
Genetics and Development at CUMC.
Alopecia areata is a common autoimmune disease that causes
disfiguring hair loss. The disease can occur at any age and affects
men and women equally. Hair is often lost in patches on the scalp,
but in some patients it also causes loss of facial and body hair.
There are no known treatments that can completely restore hair, and
patients with the disease experience significant psychological
stress and emotional suffering.
Scientists have known for decades that hair loss in alopecia
areata occurs when cells from the immune system surround and attack
the base of the hair follicle, causing the hair to fall out and
enter a dormant state. Until now, the specific type of cell
responsible for the attack had been a mystery.
A major clue was uncovered four years ago in Dr. Christiano’s
genetic study of more than 1,000 patients with the disease. That
study suggested that a “danger signal” in the hair follicles of
patients — not previously linked to alopecia areata — attracts the
immune cells to the follicle and sparks the attack.
Hair follicle (blue) being attacked by T cells
The current paper describes how the team first studied mice with
the disease, then tracked backward from the danger signal to
identify the specific set of T cells responsible for attacking the
hair follicles. Further investigation of mouse and patient cells
revealed how the T cells are instructed to attack and identified
several key immune pathways that could be targeted by a new class of
drugs, known as JAK inhibitors.
Two FDA-approved JAK inhibitors tested separately by the
researchers — ruxolitinib and tofacitinib — were able to block
these immune pathways and stop the attack on the hair follicles. In
mice with extensive hair loss from the disease, both drugs
completely restored the animals’ hair within 12 weeks. Each drug’s
effect was also long-lasting, as the new hair persisted for several
months after stopping treatment.
Together 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, the researchers
rapidly initiated a small open-label clinical trial of ruxolitinib —
which is FDA approved for the treatment of a blood disorder — in
patients with moderate-to-severe alopecia areata (with more than 30
percent hair loss). In three of the trial’s early participants,
ruxolitinib completely restored hair growth within four to five
months of starting treatment, and the attacking T cells disappeared
from the scalp.
Restored hair growth in a research subject with
Left to right: at baseline, at 3 months, and at
4 months of treatment.
“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
“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.
A practicing dermatologist who cares for many patients with
alopecia areata himself, Dr Bickers said, “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
But as Dr Christiano knows firsthand from her own personal
experience with the disease, alopecia areata is too often dismissed
as simply an appearance-altering disease. “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.”
Alopecia Areata is driven by cytotoxic T lymphocytes and is
reversed by JAK inhibition. Nature Medicine.