New Hope For Treating Common Form Of Inherited Neuromuscular Disease

[Guest guest]

New Hope For Treating Common Form Of Inherited Neuromuscular Disease

http://medicalnewscenter.com/out/out.cgi?

http://www.sciencedaily.com/releases/2008/09/080902122836.htm

Treatments that ramp up production of the tiny " motors " that power

cells may have promise for treating one of the most common forms of

inherited neuromuscular disease, according to a report in the

September Cell Metabolism.

Neuromuscular disorders caused by defects in those mitochondrial

motors affect a large number of children and adults worldwide, but

today remain without treatment, the researchers said.

The researchers now show in mice with a muscular defect in

mitochondria function that treatments designed to increase the number

of mitochondria can improve symptoms of muscle weakness and enhance

survival. Those treatments work by enhancing the activity of so-

called peroxisome proliferator-activated receptor ? (PPAR?)

coactivator a (PGC-1a), a master regulator of metabolism known to

play an important role in the production of mitochondria.

" The idea was that in the mice and in patients with these disorders,

there is still residual activity of the defective mitochondrial

enzymes, " said Moraes of the University of Miami School of

Medicine. " If per cell there were more mitochondria, each with that

same residual activity, would it improve clinical symptoms?, " he

asked.

" That's exactly what happened in the mice, " he said. " With more

mitochondria, the myopathy was milder and the mice lived longer

without symptoms. " Myopathy refers to any neuromuscular disease in

which muscle fibers fail to function properly, resulting in muscle

weakness.

In the mice with mitochondrial myopathy, the researchers induced

mitochondria production in two ways: through genetic modifications

that increased PGC-1a in skeletal muscle and by giving them a drug

called bezafibrate that is already FDA-approved for the treatment of

metabolic disorders, including elevated lipids (hyperlipidemia),

diabetes and metabolic syndrome. Bezafibrate activates PGC-1a along

with other peroxisome proliferator activated receptors (PPARs).

Both treatment approaches resulted in longer life span for the mice

and delayed the onset of their disease, they report. That effect most

likely stemmed from an increase in mitochondria. In some cases they

found mitochondria in the muscle increased by as much as four or five

times, Moraes said.

Mice with the impaired mitochondria typically live only three or four

months, he said. The transgenic PGC-1a mice lived for about one year

and some for as long as 22 months. Those treated with bezafibrate

therapy lived for at least six months, they found.

The treated animals also showed stronger performances on a treadmill.

Untreated mice with the mitochondrial defect begin to fall on

treadmill tests at three months of age. The PGC-1 a transgenic mice

with myopathy didn't show signs of falling until seven months. Those

taking the drug showed a better treadmill performance at six months

than the untreated mice did at three months.

" Controlling the expression of PGC-1a and the PPARs might offer a

novel treatment strategy not only to mitochondrial myopathies, but

also other mitochondrial diseases, " the researchers conclude from

their findings. " The promising results with the bezafibrate-fed

myopathy mice clearly identify small-molecule PPAR agonists, already

used in humans with metabolic disorders as a treatment option for

mitochondrial diseases. "

While the results are promising, Moraes cautioned that there are

potential side effects of bezafibrate that need to be examined. He

said he hopes a clinical trial to find out how well they might work

in patients with mitochondrial disorders will begin soon. They are

also doing studies to test whether a similar treatment might have

potential for treating mitochondrial disorders of the brain as well.

The researchers include Tina Wenz, University of Miami, School of

Medicine, Miami, FL; Francisca , University of Miami, School of

Medicine, Miami, FL; Bruce M. Spiegelman, Dana-Farber Cancer

Institute and the Department of Cell Biology, Harvard Medical School,

Boston, MA; and T. Moraes, University of Miami, School of

Medicine, Miami, FL.

[Guest guest]

What disease are they refering to?

Treatments that ramp up production of the tiny " motors " that power

cells may have promise for treating one of the most common forms of

inherited neuromuscular disease, according to a report in the

September Cell Metabolism.

Thanks

[Guest guest]

Hi ,

The article refers to neuromuscular diseases that are mitochondrial

in origin. CMT 2A is just this. You may want to read Dr. Chan's

research at

http://biology.caltech.edu/Members/Chan

and

http://www.its.caltech.edu/~chanlab/main%20pages/research.html

Gretchen

[Guest guest]

Hi Gretchen

Thanks for clarifying

Take care