TESTS MAY SOON PREDICT PREDNISONE RESPONSE

Prednisone and other drugs in the "corticosteroid" family (for example, prednisolone and deflazacort) can slow the downhill course of Duchenne muscular dystrophy in some boys without causing serious side effects, but, in others, the adverse effects outweigh any potential benefit from these drugs.

According to a review of the subject in the August issue of Neuromuscular Disorders, weight gain is a particularly serious problem associated with corticosteroid use in muscular dystrophy, because it can, if large enough, offset any increase in muscle strength, as well as encourage spinal curvature in boys who use wheelchairs.

Eric Hoffman of the Center for Genetic Medicine at Children's National Medical Center in Washington has been studying the problem and says he thinks the development of adverse effects such as weight gain are under genetic control. (Some other adverse effects of corticosteroids include cataracts, depression, loss of bone and striations on the skin.) Hoffman, who has had many MDA research grants, says his group has been trying to pinpoint the precise genetic differences that determine how cells handle corticosteroids.

Others agree. "If you could predict which boys would develop side effects and which would get the benefit of these drugs with minimal or no side effects, you would really have a tremendous therapeutic advantage," says MDA grantee George Karpati of the Department of Neuromuscular Research at Montreal Neurological Institute.

Karpati says he's long suspected that the differences in how people respond to corticosteroids reflect genetic factors, but that, until now, no one has undertaken a systematic study.

Corticosteroids have been used with some success in Becker muscular dystrophy and in at least one person with limb-girdle dystrophy. Prednisone wasn't effective when tested on eight people with facioscapulohumeral dystrophy. Prednisone and related drugs are routinely used in myasthenia gravis, Lambert-Eaton myasthenic syndrome, polymyositis and dermatomyositis.

McARDLE'S GENE THERAPY LOOKS GOOD IN SHEEP

Gene therapy for the metabolic muscle disorder McArdle's disease looks promising in experiments in sheep, and human trials may not be far off. That's the word from MDA grantees John Howell of the Division of Veterinary and Biomedical Sciences of Murdoch University in Perth, Western Australia, and George Karpati of the Department of Neuromuscular Research at Montreal Neurological Institute.

Howell has been injecting sheep with the gene for muscle phosphorylase, an enzyme that's missing or defective in people with McArdle's disease (also known as phosphorylase deficiency and type 5 glycogenosis).

People with the disorder can't break down the carbohydrate glycogen, a "fuel" needed for muscle contraction. They therefore have limited ability to exercise and can severely damage their muscles if they overuse them. Kidney damage can occur as a result of the muscle breakdown.

Inserting a corrected phosphorylase gene would theoretically improve their exercise capacity and protect their muscles and kidneys.

GENE THERAPY TRIALS FOR LGMD PLANNED

Plans for a gene therapy trial in limb-girdle muscular dystrophy (LGMD), a form of muscular dystrophy that involves weakness in the muscles of the shoulder and pelvic girdles and sometimes affects other muscles, are under way following a November meeting of LGMD genetics researchers.

LGMD can result from flaws in several different genes; the gene therapy trial will focus on LGMD resulting from flaws in any of four genes for muscle proteins known as sarcoglycans.

Safety testing of gene therapy using the sarcoglycan genes is expected to begin this spring at the University of Pennsylvania under the direction of physician-researchers James Wilson and Hansell Stedman, and at Ohio State University under neurologist Jerry Mendell, co-director of the MDA clinic at that institution. Several other institutions will be involved in genetic testing of people with symptoms of LGMD. For information, call MDA at (800) 572-1717.

GENETIC TEST NOW AVAILABLE FOR FSHD

Genetic testing is available for many genetic neuromuscular disorders, but usually such tests have to wait for a specific gene underlying a disease to be identified.

No such gene has yet been identified for facioscapulohumeral muscular dystrophy (FSHD), a muscle-wasting disorder of variable severity that affects the face, shoulders and upper arms and sometimes involves other muscles. However, the absence of a stretch of DNA on chromosome 4 that doesn't contain genes but probably influences whether some genes are made into proteins by the cell has been closely associated with FSHD.

Now, the University of Iowa's Department of Molecular Pathology is offering a test to detect this DNA segment which is considered highly reliable, for $388. Have your doctor call Beth Alden at (319) 384-9568 for details on how to draw and send a blood sample to Iowa. Results will be reported to your doctor.

Two Canadian centers -- Alberta Children's Hospital in Calgary and Children's Hospital of Eastern Ontario in Ottawa -- are also offering FSHD testing. The genetic counselor associated with your MDA clinic is a good source of up-to-date information on genetic tests.

ALTERNATIVE MEDICINE'S 'FREE RIDE' CHALLENGED

"It is time for the scientific community to stop giving alternative medicine a free ride," writes Marcia Angell, executive editor of the New England Journal of Medicine, and Jerome Kassirer, its editor-in-chief, in the Sept. 17 issue.

"There cannot be two kinds of medicine -- conventional and alternative," the physicians write. "There is only medicine that has been adequately tested and medicine that has not, medicine that works and medicine that may or may not work."

The editors say that, once a treatment has been adequately tested and found safe and effective, it doesn't matter whether it was originally considered "alternative" or not. What matters is the testing process.

Several examples of harm resulting from ingestion of over-the-counter, unregulated and untested dietary supplements (particularly herbal remedies) are reported in a large section on alternative medicine in the same issue.

Angell and Kassirer decry the 1994 passage of the Dietary Supplement Health and Education Act, which made substances considered dietary supplements nearly exempt from Food and Drug Administration regulation. The editors found that some of these products were contaminated with poisons, such as lead, arsenic and mercury; some contained potent drugs and biologically active molecules, such as digitalis (a heart medication) and hormones; and some contained none of the active ingredient appearing on the label.

NEW TRIAL OF BDNF FOR ALS

In the new trial, BDNF will be administered via a thin tube connected to an electronic pump into the fluid surrounding the spinal cord ("intrathecal" administration). The pump itself (round part) is usually placed under the skin in the abdominal area. Photo courtesy of Medtronic.

The pharmaceutical companies Amgen (Thousand Oaks, Calif.) and Regeneron (Tarrytown, N.Y.) have announced the opening of a new trial of BDNF for amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease).

BDNF -- brain-derived neurotrophic factor -- was previously tested and found ineffective in ALS, a rapidly progressive and fatal disorder that involves death of muscle-controlling nerve cells in the brain and spinal cord. However, the new trial will administer the experimental drug directly into the fluid surrounding the spinal cord, in contrast to the previous trial, in which it was given as subcutaneous (under the skin) injections. The delivery method is an attempt to improve the absorption of BDNF by the nerve cells that are affected in ALS.

The experimental drug is based on a natural substance that improves survival of nerve cells subjected to adverse conditions in laboratory experiments.

The trial will be conducted at 16 centers in the United States and Europe, will last 18 months and will be placebo-controlled (meaning one group will be given an inert substance and be compared with the group receiving BDNF).

For general information about the trial, call Amgen's information line at (800) 772-6436. You can also check Amgen's Web site, www.amgen.com. The U.S. trial sites are: