Research Updates July-August 2007

Article Highlights:

Research updates as of June 2007

by Margaret Wahl on July 1, 2007 - 10:32am

QUEST Vol. 14, No. 4

Experimental compound shows promise for SBMA

A compound known as ASC-J9 has shown promising effects in treating spinal bulbar muscular atrophy (SBMA), also called Kennedy’s disease, in mice with the disorder. Mice treated with ASC-J9 dissolved in corn oil and injected into the abdomen every other day showed better motor and sexual function and longer survival than mice treated with a corn oil solution alone. The treatment was effective whether it was given before the onset of symptoms or long after.

SBMA, which affects males almost exclusively, is a disease in which muscle-controlling nerve cells (motor neurons) in the spinal cord and brain stem degenerate. Feminization and impairment of fertility and sexual function may also occur.

The root cause of the disease is an expanded section of DNA in the gene for the androgen receptor, a protein that normally transports male hormones (androgens) inside cells.

The expanded DNA leads to an expanded, sticky androgen receptor protein that forms clumps in the nuclei of nerve and muscle cells. Trapped inside the clumps are a number of proteins that would otherwise regulate various cellular functions.

Zhiming Yang at the University of Rochester (N.Y.) Medical Center, and colleagues, who published their results in the March issue of Nature Medicine, say they believe ASC-J9 disrupts this abnormal clumping.

Diane Merry at Thomas Jefferson University in Philadelphia, who’s had MDA support for SBMA research, was part of the research team.

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Female muscle stem cells work better

Stem cells taken from the muscles of healthy mice and transplanted into the muscles of mice with a disease resembling Duchenne muscular dystrophy (DMD) are more effective at causing muscle regeneration if they’re taken from female donors instead of male donors, say investigators at Children’s Hospital of Pittsburgh, the University of Pittsburgh and the University of California-Los Angeles.

Researchers in the laboratory of Johnny Huard at the University of Pittsburgh, who published their findings in the April 9 issue of the Journal of Cell Biology, say they think the difference may be caused by “innate sex-related differences in the cells’ stress responses.” Huard received MDA support for this work.

Their experiments, they say, show that the superior regenerative abilities of the female-derived stem cells probably isn’t directly related to hormonal factors or to a difference in the immune response to male versus female cells.

Instead, they say, it seems to be related to the female-derived stem cells’ propensity for staying immature and proliferating for the first three days or so after transplantation, while the male-derived cells tend to mature (differentiate) immediately into muscle cells.

After three days, they say, the environment in which the new cells find themselves becomes more hospitable, with less inflammation and more oxygen available. The female cells, many of which will have survived and proliferated during the early phase of transplantation, can then differentiate, fusing with muscle fibers and causing them to regenerate.

But by this time many of the male cells will have already matured in the more hostile circumstances and been killed by cellular defenses, leading to the regeneration of a smaller number of muscle fibers.

The new findings, Huard said, “may shed light on the conflicting results in the literature on stem cells, since in many instances the gender of the [recipients] and the donor are not even characterized.”

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