[tt] [wta-talk] New drugs that mimic mutations found in buff animals could treat muscle-wasting diseases

Fri Oct 19 06:48:52 UTC 2007

----- Forwarded message from James Clement <clementlawyer at hotmail.com> -----

From: James Clement <clementlawyer at hotmail.com>
Date: Thu, 18 Oct 2007 15:02:34 -0700
To: 'World Transhumanist Association Discussion List' <wta-talk at transhumanism.org>
Subject: [wta-talk] New drugs that mimic mutations found in buff animals
	could treat muscle-wasting diseases
X-Mailer: Microsoft Office Outlook 12.0
Reply-To: World Transhumanist Association Discussion List <wta-talk at transhumanism.org>

Thanks to Dr. Derya Unutmaz for bringing this article to my attention.  This
definitely has "enhancement" written all over it!  Go to the website for a
picture of a "buff" dog! http://www.technologyreview.com/Biotech/19589/

TECHNOLOGY REVIEW (MIT)
Thursday, October 18, 2007
Mimicking the Massively Muscular
New drugs that mimic mutations found in buff animals could treat
muscle-wasting diseases.
By Emily Singer

Scattered throughout the mammalian menagerie are a few supermuscular freaks:
double-muscled cows more ripped than any bodybuilder; racing dogs too burly
to run; sheep praised for their massively muscled buttocks; and even one
small German boy, born in 2000 with muscles twice the size of those of a
normal newborn. All these Herculean creatures share one thing: naturally
occurring mutations in a gene that produces myostatin, a protein that blocks
growth of skeletal muscle. Disable that gene, and viola--spectacular muscle
growth results. 

Over the past few years, pharmaceutical companies have been racing to
develop ways to mimic myostatin gene mutations in the hope of treating
everything from the muscle loss that accompanies muscular dystrophy, cancer,
and aging to obesity and other metabolic disorders. Pharmaceutical giants
Wyeth and Amgen are expected to release clinical-trial results of myostatin
inhibitors for muscle-wasting diseases within the next few months. A smaller
company, Acceleron Pharma, based in Cambridge, MA, says that its more
broadly acting drug could bring more brawn than can drugs targeting
myostatin alone.

"There's been a huge amount of interest for human therapeutics," says Se-Jin
Lee, a biologist at John's Hopkins University, in Baltimore. "If you could
increase or maintain muscle strength as people age, you could have a
tremendous impact on health and well-being."

Lee discovered more than a decade ago that mice lacking myostatin grew
muscles twice the size of those of their normal counterparts. But because
mice have levels of myostatin 50 to 80 times that of humans, some scientists
have doubted how well the results will translate to humans. New findings
published in August in the journal PLoS ONE suggest that other molecules are
also at work in muscle. Lee found that he could double the extra growth in
mice lacking myostatin--effectively quadrupling muscle mass--by turning up
levels of another protein. "That means there must be other regulators that
have at least as important a function as myostatin in blocking muscle
growth," says Lee.

Mighty muscles: The image shows the difference between normal mice (left)
and mice that lack myostatin and overproduce another protein, giving them
four times as much muscle. Scientists are developing drugs that act through
similar mechanisms to treat muscle-wasting diseases.
Credit: Se-Jin Lee, Johns Hopkins University School of Medicine

Acceleron's approach attempts to take advantage of that. Rather than
designing an antibody to myostatin itself, as is being tested in the Wyeth
trials, scientists at Acceleron fused a portion of the receptor molecule
that usually binds to myostatin with a tag that allows the drug ACE-031 to
roam freely throughout the body so that it can sop up myostatin before it
activates the signal to stop muscle growth. Animal studies show that this
approach boosts muscle growth more effectively than does merely eliminating
myostatin, suggesting that the fusion molecule also binds to other agents
that impact muscle development. 

Normal mice given the drug show a 30 to 60 percent increase in muscle mass,
and mice with a version of muscular dystrophy show increased grip strength,
a standard measure of rodent strength. Preliminary results from primate
studies show that the animals on the drug bulk up at similar rates to those
seen in rodents. "Before I became involved with Acceleron, if someone had
told me you could increase muscle mass by up to 60 percent in a month, I
never would have believed it," says CEO John Knopf. 

While it's not yet clear if similar rates will be seen in humans, high doses
of anabolic steroids, which carry serious side effects, increase muscle mass
by a maximum of 15 to 20 percent. And because myostatin is found only in
muscle, knocking it out does not appear to have the adverse effects of
broader-acting steroids.

Acceleron plans to begin trials of its drug for muscular dystrophy, a
genetic disorder of progressive muscle loss that usually kills sufferers
before they reach age 30, in early 2008. Trials for cancer and ALS will
follow. 

Acceleron's Big Pharma competitors are farther along. In 2005, Wyeth,
headquartered in Madison, NJ, began a clinical trial of an antibody to
myostatin that binds to it and blocks its activity, as a treatment for two
forms of muscular dystrophy. Results were expected to be released late last
year, but the company declined to comment on the current status. Amgen,
headquartered in Thousand Oaks, CA, is analyzing results from a recently
completed safety trial of its own myostatin inhibitor. The company is also
testing a second inhibitor as a countermeasure to space-flight-induced
muscle changes. Mice aboard the Space Shuttle Endeavor in August were given
Amgen's experimental drug to determine if it could slow muscle loss in
microgravity.

While initial clinical trials are focused on relatively rare conditions such
as muscular dystrophy, safe muscle-building drugs have a broad potential
market. "There is no effective agent to prevent the accelerated loss of
muscle associated with disease, infection, or illness, such as cancer, heart
failure, and kidney disease and dialysis," says William Evans, director of
the Nutrition, Metabolism, and Exercise Laboratory at the University of
Arkansas for Medical Sciences. Muscle loss is linked to increased mortality
in these patients, as well as to an individual's level of disability
resulting from normal aging. "As treatments of disease like cancer and heart
failure become more effective, the issue becomes more prominent," says
Evans. For example, treating cancer patients with a muscle-building drug may
allow oncologists to administer extra rounds of chemotherapy. 

In addition to treating muscle wasting, such drugs might prove effective in
treating metabolic disorders, such as insulin resistance, which is linked to
obesity and diabetes. Previous research has shown that diet-induced obese
mice given Acceleron's drug showed an increase in lean muscle mass and
reduced fasting glucose and insulin levels. Says Evans, "I think these
drugs, perhaps used in combo with exercise, might have great potential in
reversing the trend toward increasing obesity and decreasing muscle mass."

--------------------------
James Clement, J.D., LL.M.

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