Thursday, August 28, 2008

Biogen Idec Testing Regenerative Medicine Drug to Reverse the Path of
Multiple Sclerosis
Luke Timmerman 8/27/08

Biogen Idec has made a lot of its money on Avonex and Tysabri, drugs
that slow down the rate of flare-ups for people with multiple
sclerosis. Now the Cambridge, MA-based biotech company (NASDAQ: BIIB)
is pursuing a loftier goal. It is working on the first experimental
drug that may reverse the symptoms of the neurodegenerative disease.

The drug, being tested in animals and prepped for its first human
trial, is designed to block a protein called Lingo-1 that interferes
with body's production of myelin, the fatty protective coating around
nerve fibers. People with multiple sclerosis have an overactive immune
system that eats away at the myelin layer, and they have no ability to
regenerate myelin in the brain or spinal cord, says Sha Mi, a Biogen
researcher. That means nerve impulses that control speech, vision, and
movement get short-circuited, sort of like when an electrical wire is
stripped of its insulation. Biogen thinks it now has engineered a drug
that can stop Lingo-1 from doing its dirty work, allowing the body to
regenerate myelin coating around nerves. That could restore normal
functions, like walking.

"People around the company are very excited about this," says Kenneth
Rhodes, Biogen's vice president of discovery neurobiology. "It's
potentially a transformational therapy." Sha Mi, the Biogen scientist
who discovered the molecular switch that paved the way for the
program, put it this way, "As a scientist, I came all the way from
China. If we can create a new medicine to affect patients, that is my

The drug hasn't even entered clinical trials yet, and it's already
been an eight-year odyssey. Sha Mi (who goes by the name Misha) joined
the company in 2000 from Wyeth's Genetics Institute unit in Cambridge,
MA. Not long after joining Biogen, she found the Lingo-1 protein in a
database and learned it was expressed solely in the central nervous
system and, then, only in neurons. Later experiments showed that when
scientists delete the gene that makes Lingo-1 in mice, those altered
mice would recover from a disease in which the immune system eats away
at myelin, called autoimmune encephalomyelitis. The same recovery was
seen in mice when they were given an antibody drug designed to block
the Lingo-1 protein. There were no side effects or dangers seen from
producing too much myelin, because the body will only produce the
amount needed to cover nerves, Sha Mi says. The combination of
experiments, conducted by Biogen scientists and collaborators in
China, made the cover of Nature Medicine last October.

Other researchers are working on myelin repair, such as a group led by
Bruce Trapp at the Cleveland Clinic, says Rhodes, the Biogen vice
president. Madison, NJ-based Wyeth (NYSE: WYE) has attempted to
develop conventional small molecule drugs against Lingo, but hasn't
been successful, he says.

Biogen is developing a genetically engineered antibody against Lingo
because that approach should do a better job of binding with the Lingo
protein target on the surface of cells, Rhodes says. The first
version, however, wasn't quite "optimal," and a newer one is being
engineered with better properties, he says. The latest version is made
with fully human DNA, instead of partial mouse DNA, because
researchers want to be confident that the drug won't spark the immune
system to reject it, especially if it needs to be given chronically.
The company is planning to ask the FDA for permission to start its
first human clinical trials, although he wouldn't say when.

No details are available yet on how the trials will be crafted, but
Rhodes made clear that the company's vision is for Lingo to be used in
combination with Avonex or Tysabri. The idea is that those drugs can
reduce the immune system's assault on neurons, quieting the storm.
That would give an opportunity for the anti-Lingo-1 drug to step in
and regenerate myelin around the nerves.

Since 400,000 people in the U.S. suffer from MS, and there's nothing
else quite like this program poised for clinical trials, it seems
unlikely that Biogen will have much trouble recruiting patients in the
first study. If they show they can regenerate myelin in even a few
people, Biogen will be a few steps closer to fulfilling Sha Mi's dream.\


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