A search of pubmed.org faustman + tnf will reveal that suppressing the immune system is not always a sound approach and that increasing the level of TNF alpha has many useful therapeutic applications.
The genes and cytokines and pathways thought to be involved below were not described in detail for our consideration and pondering.
aureen Dowd
The
first thing Brian H. noticed was that he could grow a real beard. It
had been years since that had been possible, years he spent bedeviled by
hair loss on his head, face, arms and legs.
Brian, 34, who asked that his last name be withheld to protect his privacy, suffers from alopecia areata,
an autoimmune disease afflicting about 1 percent of men and women,
causing hair to fall out, often all over the body. He believes that the
“mangy patches” of baldness that have plagued him since his 20s have
cost him jobs and relationships.
After
trying various treatments, Brian enrolled this year in a study at
Columbia University Medical Center testing whether a drug approved for a
bone marrow disorder could help people with alopecia. One of the
study’s leaders, Angela Christiano, is a dermatology professor and
geneticist who herself has alopecia areata.
After
successfully testing on mice two drugs from a new class of medicines
called JAK inhibitors, which suppress immune system activity by blocking
certain enzymes, the researchers began testing one of the drugs,
ruxolitinib, on seven women and five men. Some of their findings were published Sunday in the journal Nature Medicine.
The results for Brian and several other participants have been significant.
“Pretty
quickly, there were sort of fringes,” Brian said. Then “three or four
large areas started to show hair growth,” and by five months, he had
plenty of hair on his head, arms, and even his back. “I was blown away,”
he said.
The
disease differs from other types of hair loss, including male pattern
baldness, and there is no evidence the drug will work for those
conditions. Experts caution that even for alopecia areata, it is too
early to know if the treatment will work for most patients and if there
are significant side effects or safety concerns.
The
study is continuing, but so far a few participants did not regrow hair,
said Dr. Julian Mackay-Wiggan, director of Columbia’s dermatology
clinical research unit and an author of the study.
“It
appears to work — not in everyone, but in the majority,” she said. “We
need a lot more data on the long-term risks in healthy individuals. But
it’s certainly very exciting in terms of hair growth. It was surprising
how quickly and impressively the growth occurred.”
Dr.
Luis Garza, a dermatologist at Johns Hopkins Hospital who was not
involved in the research, said the results were encouraging enough that
he would consider prescribing ruxolitinib to patients who could not be
treated with other methods and who understood potential side effects.
Cortisone
injections often work for patients with isolated patches of baldness,
but they must be done regularly and are painful. For patients with
severe baldness, “it’s impossible to inject their whole scalp,” he said.
“There’s a major need for improving the treatment,” he added. “It’s not ludicrous to try on a patient.”
But
Dr. George Cotsarelis, a dermatologist at the University of
Pennsylvania, urged caution until further research is conducted. He said
it makes sense that drugs suppressing immune system activity would work
for a disorder caused by an overly active immune reaction.
But
because patients in the study received twice-daily pills that
circulated ruxolitinib throughout their bodies, rather than topical
cream, he said they were “treated systemically with a very toxic drug”
that can cause liver and blood problems, infections and other ailments.
Although
the patients have experienced few side effects, the study is small and
not a randomized trial comparing ruxolitinib to other treatments.
If
ruxolitinib could be applied topically, Dr. Cotsarelis said, “this
would be an amazing breakthrough.” Until then, “patients are going to
rush in demanding this treatment, and I would not give it.”
Dr.
Raphael Clynes, a co-leader of the research while he was a Columbia
professor (he now works for Bristol-Myers Squibb), said the team tested
cream and pills on mice, and planned to test a cream on people.
So
far, he considered ruxolitinib “an expensive therapy that’s probably
effective based on the small number of patients that we’ve treated, and
it’s likely to have a reasonable safety profile. But there’s no way that
I can endorse it fully unless we do larger trial.”
The
team also plans to test on people another JAK inhibitor, tofacitinib,
which is approved for rheumatoid arthritis and grew hair on mice. In
June, Dr. Brett King, a dermatologist at Yale, reported that tofacitinib
caused full hair growth and no negative effects for a man with alopecia
universalis, a variant involving almost total hair loss.
The
idea to use JAK inhibitors grew out of a genome analysis Dr. Christiano
conducted, which found that in alopecia areata, hair follicles emit a
signal that draws immune cells to attack. Her team identified specific
cells involved and found genetic similarities to unrelated autoimmune
diseases, like rheumatoid arthritis.
Several
of the 12 patients are still completing the study, taking ruxolitinib
for three to six months. Dr. Christiano has not tried it because, she
said, her alopecia has been dormant, although “I have an eyebrow that
comes and goes.”
For
Brian, five months on the drug yielded a full head of hair. For unknown
reasons, the new hair is white instead of black, its original color.
Still,
“It’s a lot easier to shrug that off than to pass the silent judgment
of people” who he said he felt were staring at his bald splotches. He
said side effects, including slight anemia, were minor.
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