Johns Hopkins scientists have found yet another reason
why you should listen to your mother
when she tells you to eat your vegetables. Sulforaphane, a
chemical present at high levels in a
precursor form in broccoli and related vegetables
(cauliflower, Brussels sprouts, etc.), helps prevent
the severe blistering and skin breakage brought on by the
rare and potentially fatal genetic disease
epidermolysis bullosa simplex, known as EBS.
The researchers treated newborn mice that had a severe
form of EBS with a topical solution
containing sulforaphane and found marked improvement.
Untreated mice all died within three days, but
after four days, more than 85 percent of the treated mice
were alive and blister-free. These findings
appeared online Aug. 27 in Proceedings of the National
Academy of Sciences.
The basis of EBS, notes study author Pierre Coulombe,
biological chemistry, lies in
two specific genes that make proteins known as keratins.
Normally, the keratins join together and
form highly resilient fibers in the lower portion of skin,
helping make it durable. If either keratin is
defective, they don't mesh and the lower skin tissue
becomes unusually fragile and gets damaged from
the mildest mechanical stress — leading to blistering
pain, a higher risk of infection and in the most
severe cases, death.
"Humans have around 54 distinct keratins, many of
which are similar in structure and function,"
Coulombe said. "We figured we might be able to exploit this
similarity and dial up a replacement by
triggering the activation of a suitable signaling pathway
in skin." He predicted that sulforaphane might
stimulate the formation of a surrogate skin-strengthening
keratin to stand in for the defective one.
The desire to learn more about sulforaphane led
Coulombe and his co-workers to Paul Talalay,
pharmacology, who had previously identified
sulforaphane as a cancer-preventive agent.
"It turns out that treatment with low doses of sulforaphane
triggers the expression of selected
keratin genes in skin," Coulombe said. "So we began what
evolved into a highly rewarding collaboration
and found it does indeed work in a mouse model for EBS."
"This is the first suggestion that we may be able to
treat this terrible disease," said Talalay, a
co-author of this study. "And we didn't need to invent a
new drug; sulforaphane is naturally found in
The team will next test whether sulforaphane can
stimulate the proper keratin protein in the
appropriate subset of human skin cells, a vital matter for
any future medical hopes. Beyond that are
issues of how effective a topical application would be on
human skin, which is considerably thicker than
mouse skin, and examining the long-term effects of
"If we can clear these important hurdles, then
sulforaphane can potentially be a tremendous
therapeutic, with the added benefit of having anticancer
properties," Coulombe said. "And when you
consider that the only current option for EBS is wrapping
gauze around trauma-prone areas to
minimize breakage, and otherwise avoiding infection and
making sure blisters heal properly, then even
a mild success would be a significant benefit for these
The research was funded by the National Institutes of
Health, March of Dimes Birth Defect
Research Foundation, American Institute for Cancer Research
and Lewis B. and Dorothy Cullman
Authors on the paper are Michelle L. Kerns, Daryle
DePianto, Albena T. Dinkova-Kostova, Talalay
and Coulombe, all of Johns Hopkins.