By Roni Rabin
Copyright © 2004, Newsday, Inc.
November 9, 2004

My father always used to say, "When you've got your health, you've got everything."

Then one morning, when he was 45, he went out to pick up the morning paper. As he walked down the driveway, he noticed his toes were dragging, and he had to raise his feet to avoid tripping. Anyone else might have been irritated. He was terrified.

The sudden weakness was foot drop, and for him it was the first symptom of a horrible disease: amyotrophic lateral sclerosis, or Lou Gehrig's disease, a progressive disorder that slowly paralyzes the body, destroying the motor neurons - nerve cells that carry electrical impulses from the brain and spinal cord to the muscles.

My father, David, was a physician and researcher who taught medicine at Vanderbilt University in Nashville, Tenn. He had studied neurology in medical school and still had vivid memories of ALS patients he had seen years earlier. Though he went through a series of tests, I think he suspected the diagnosis even before doctors at the Mayo Clinic confirmed it.

It was 1979. The disease was a mystery, and there was no cure. People lived an average of five years after diagnosis.

There were no approved medications, little research funding and hardly any clinical trials of potential treatments.

Over the next few years, my father started walking with a cane, then a walker. Eventually, he used a wheelchair. He was intent on maintaining his strength through exercise, and swam laps even when he could barely walk to the edge of the pool. He went into his office and lab and continued doing research. When he lost the use of his arms, he dictated papers (and an entire medical textbook).

When he couldn't speak, he used the muscles of his forehead and eyebrows to manipulate a switch on a visor that was connected to a specially designed word processing program. He was determined to see my youngest sister graduate from high school, and he often wrote my mother and three siblings notes of encouragement - with his eyebrows.

Twenty years have passed since he succumbed to ALS in 1984. In recent years, ALS has been in the news because of the high rate of illness among Gulf War veterans. And as my family marked the anniversary last month, I wondered whether science had made a dent against this killer.

Not much has changed for patients - the disease is as devastating as ever. What has changed is that ALS has become a focal point of investigation for medical scientists. The turning point came in 1993, when the first gene linked to ALS was identified. Although only about 5 percent of all cases are familial, and the identified gene is responsible for only a fraction of them, the discovery led to development of a mouse model for ALS.

This was a milestone that meant new compounds could be tested on lab mice, and it had the effect of creating a "critical mass" of scientific information that drew bright, young researchers to the field, officials with the ALS Association, a national nonprofit organization, told me. Unfortunately, many of the drugs that worked on mice didn't work in humans.

In 1995, the FDA approved the first medication to treat ALS, Riluzole, which slows progression of the disease somewhat. But it only extends survival by a few months. And there have been setbacks: Recently, for example, a major clinical ALS trial of the arthritis drug Celebrex, which appeared promising in animals, showed no effect in humans.

But several other large, national clinical trials are actively recruiting ALS patients to test promising compounds. That's a major change, said Dr. Hiroshi Mitsumoto, director of the ALS center at Columbia University Medical Center. The National Institutes of Health didn't fund clinical trials until probably five years ago, Mitsumoto said. "Now, we have three or four clinical trials, and even more are coming."

Compounds being tested include minocycline, an antibiotic that inhibits pathological cell changes; insulin-like growth factor 1, which seems to protect motor neurons in animals; creatine, a naturally occurring chemical involved in energy production in the muscle; and creatine monohydrate, which showed positive results in a trial of 21 patients.

Stem cell research also has potential. Scientists think they may be able to transplant stem cells to replace the diseased cells. And another developing technology, gene therapy, has increased survival in mice when the gene encoding insulinlike growth factor was delivered into the motor neurons.

New insights into ALS also reveal similarities to Alzheimer's and Parkinson's: abnormalities such as the accumulation of proteins in the cells. The commonalities make for synergy in research and make research more attractive to biotech and pharmaceutical companies.

Still, the bottom line hasn't changed 20 years after my father's death: The average life expectancy for ALS patients is still five years. For patients and their families, that's all that really matters.

My father might have seen it differently. An optimist, he believed in the scientific process, the step-by-step accumulation of knowledge that is eventually translated from the bench to the bedside. The method resembles assembling a giant puzzle piece by piece, Mitsumoto said. "We have many of the pieces, but something crucial is still missing."