Matthew Herper
A brawny infant's mutation has set off a hunt for a muscular dystrophy drug.
The child was the talk of the Neonatal Ward at Charite Hospital in
Berlin, Germany. His biceps and and thighs were twice as thick as a
normal newborn's despite typical height and weight. He looked like he'd
been lifting weights in the womb. This was in 2000. The child's
doctor called in pediatric neurologist and geneticist Markus Schuelke.
He thought the boy might have had a muscular disease but then
remembered that Se-Jin Lee, a Johns Hopkins University geneticist, had
produced overly buff mice by knocking out the gene for a protein called
myostatin, which is supposed to slow muscle growth. Schuelke thought
here was the first evidence of a myostatin mutation in a human. Four years later the world heard about the boy for the first time,
when a group of researchers including Schuelke and Lee proved the boy
had a myostatin mutation. By then the child could hold a 7-pound
dumbbell in each of his outstretched hands. One writer to the New England Journal of Medicine speculated that the mythical Hercules was a myostatin mutant, too. The
news about this rare mutation precipitated an intensive effort to
design drugs--call them myostatin blockers--that would let muscles
flourish without onerous side effects. The work holds the most promise
for patients with Duchenne muscular dystrophy, a debilitating and
deadly disease diagnosed in 600 American children, almost all boys,
every year. Corticosteroids and heart-failure drugs have allowed some
patients to survive into their 40s, but they are still strapped to
ventilators and require round-the-clock care. "This is a like a
bright light in a fairly dark tunnel," says Patricia Furlong, founder
of Parent Project Muscular Dystrophy. She lost two teenage sons to
Duchenne. The research also offers hope for patients with Lou Gehrig's
disease and age-related weakening. Myostatin was discovered in
mice in 1992 in Lee's Johns Hopkins lab. In 1996 he proved its
importance by showing that mice without the myostatin-producing gene
got twice as big. The next year he discovered that the bulging Belgian
Blue cow was a myostatin mutant, the first of eight prized cattle
breeds later found to have the mutation. The company he had cofounded,
MetaMorphix, is working on manipulating myostatin to beef up livestock.
Wyeth
(nyse:
WYE -
news
-
people
)
picked up the rights to develop a drug for humans. Its experimental
antibody drug produced bulked-up mice in 2002, and results of a trial
in adults with muscular dystrophy are expected as early as March. Already
there are concerns that the drugs might be used by athletes as a kind
of supersteroid, and dietary-supplement companies have introduced
knockoffs made from sea algae for that purpose. "They don't work," says
Schuelke. Schuelke and Lee still see room for failure. Side
effects could crop up, and Lee's work shows that real muscle growth may
require a broader attack than the Wyeth drug's targeted approach,
because there are a host of mysterious myostatin-like proteins that
also dampen muscle growth. Lee doesn't know how many. Acceleron Pharma
is set to begin human trials on a drug that mimics a cell receptor that
could disable many of the myostatin-like proteins. The Cambridge, Mass.
firm has raised $56 million from venture funds, including Polaris
Venture Partners and OrbiMed Advisors. Schuelke continues to see
the muscular boy he found in Berlin seven years ago. Though there were
fears that his heart might get too thick, the boy is completely
healthy. He's strong but no longer abnormally so. It may be that
myostatin's effects are most dramatic during fetal development, but
that's one of many guesses in this genetic mystery.
Source Forbes.com
|