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21
Baldness
Breakthrough
Scientists learning
to generate new hair
follicles
by Angela S. Hoover, Staff Writer
Although balding affects both
men and women, men are hit the
hardest by male-pattern baldness,
or androgenetic alopecia. It strikes
genetically predisposed individuals when a byproduct of testosterone called dihydrotestosterone
(DHT) causes hair follicles on the
scalp to shrink, producing everthinning hairs until the follicles
eventually lose the capacity to
produce hair that protrudes above
the surface of the skin.
Presently, there are only two
FDA-approved treatments for
male-pattern baldness: minoxidil
(Rogaine), a vasodilator believed
to prevent or slow follicle miniaturization by increasing nutrient
supply, and finasteride (Propecia),
which works by blocking the
conversion of testosterone into
DHT. Research has shown both
can prevent or slow hair loss and
sometimes induce regrowth by
rescuing follicles that have begun
to miniaturize. But neither can
revive totally shrunken follicles.
The only solution for this has been
relocating healthy follicles to barren patches via invasive, expensive
hair-transplant procedures.
In the fall of 2013, researchers
successfully identified molecular
pathways that can be manipulated
to generate new hair follicles.
First considered possible in the
1950s when researchers observed
new hair follicles forming during wound healing in rabbits
and mice, the work
was discredited
until 2007,
when
dermatolo-
gist George Cotsarelis from the
University of Pennsylvania’s
Perelman School of Medicine spotted hairs growing in the middle
of small cuts made into the skin
of adult mice. Cotsarelis and his
colleagues determined these were
de novo hair follicles formed in a
process that looked a lot like embryogenesis. The wound-healing
process causes skin cells to dedifferentiate, providing a limited time
window during which those cells
can be persuaded to form new hair
follicles.
In addition, inhibiting Wnt signaling during this window reduced
follicle neogenesis, while overexpressing Wnt molecules in the skin
increased the number of new follicles, according to a 2007 report in
the journal Nature. (Wnt are signal
transduction pathways that regulate cell-to-cell interactions during
embryogenesis). Cotsarelis and
his colleagues had discovered a
potential way to generate new hair
follicles. He formed a company
called Follica in 2006 to develop
new combination therapies to
induce follicle neogenesis.
Follica has patented a minimally
invasive “skin perturbation” device
that removes the top layers of skin,
causing the underlying skin cells
to revert to a stem-like state, after
which a molecule is applied topically to direct the formation of new
hair follicles. Preclinical and clinical trials have all resulted in new
hair follicles in mice and humans.
But Cotsarelis’ group has also
learned that a protein called fibroblast growth factor 9 (Fgf9), which
is secreted by gamma delta T cells
in the dermis, plays a key role in
the formation of new follicles during wound healing in adult mice.
Fgf9 still needs to be tested on
human skin in xenograft models
and then in the clinic. There’s still
a long way to go, but now there is
real hope for banishing
baldness.