Patients Desperately Seek Cure for Lou Gehrig’s Disease : Research: Thousands of sufferers are hoping for a miracle when the FDA begins testing neurotrophic growth factors.

NEW YORK — At 21, James Duncan was 225 pounds of muscle. He loved a good game of soccer, and the weights in his room never gathered dust. But his active life was forever changed last year by the mysterious muscle-wasting disease that killed baseball great Lou Gehrig.

For Duncan, it started with weak knees. Within six months, his legs no longer worked. Today, the 22-year-old is paralyzed and communicates only through slight movements of his head in his hospital room at Worcester County Hospital in Massachusetts.

His father has offered to let him die--to unplug the respirator that keeps him alive, to stop feeding him through tubes.

But the young man told his father he had a reason to live. Like thousands of other patients with amyotrophic lateral sclerosis, or ALS, Duncan is hoping for a miracle. Their hopes rest on experimental drugs called neurotrophic growth factors, substances that in animal tests have seemed to slow the killing of motor neurons by this fatal, incurable disease.

“There’s a belief that these growth factors are curative,” said Dr. Lewis P. Rowland, head of the ALS center at Columbia Presbyterian Medical Center. “Everyone is so desperate that this is going to work. It has to be tried.”

But this moment of hope is also one of anguish.

Two of the growth factors are about to enter nationwide human trials, the next step in a long process toward possible federal approval. Fewer than 1,000 of the nation’s 30,000 ALS patients will be eligible for the trials. Not all the patients in the trials will actually get the drugs. And even if the results are good, they may come years too late for people like Duncan.

So, in the meantime, patients and doctors are bombarding drug companies and the U.S. Food and Drug Administration with letters and phone calls demanding that they be included in the trials and that the trials start immediately. Others are trying to get the drugs elsewhere, hoping to forgo the experimental game of chance that will leave half the test subjects taking placebos.

“I think patients feel they are being deprived,” said Dr. Stanley Appel, head of the ALS research center at Baylor College of Medicine in Houston. “We have been telling patients since September (about the clinical trials), and they are ready. Patients want to do what AIDS patients have done. Lie down in Washington until somebody listens. This is a lethal disease for which there is no known treatment. Patients are desperate and willing to assume risks.”

FDA officials say they are moving as fast as they responsibly can. Dr. Robert Temple, FDA’s director of drug evaluation, said the agency is awaiting further safety information from recent smaller studies designed to set safe dosage levels. The larger trial, he said, “will be starting within a modest number of weeks.”

Temple said the FDA had sped up the testing process for neurotrophic factors, as it did with AIDS drugs. That’s because of their strength in animal experiments and the lack of treatment for the fatal condition.

With some AIDS drugs, the FDA has also allowed wide use before human testing was complete. But with the growth factors, Temple said, there is no human evidence yet to hint that these drugs have value.

“We are used to the idea that bad diseases allow researchers to take significant risks, but you need some evidence from humans that it is going to work,” he said. “It’s fashionable to think that some people with bad diseases just have nothing to lose. This is not the reality. You could be made sicker. It could make you die sooner.”

He added that if such evidence exists, the federal agency generally gives a drug IND (investigational new drug) status, which means it can be given on a limited or compassionate-use basis even during the study period.

“If the first ALS patients get very strong and start walking, you will see wide use of these drugs very quickly,” Temple said.

Some doctors and patients counter that any drug is worth trying for a terminal illness.

“I had a patient who died on me. I argued with the FDA. I think you should be allowed to use these experimental drugs for patients who are dying,” said Dr. Beatrice C. Engstrand, a neurologist who treats ALS patients and tried to get the growth factors. “What have we got to lose?”

About 30,000 Americans are living with ALS, and 5,000 more are diagnosed every year. The disease destroys motor neurons in the brain and spinal cord, triggering muscle weakness end finally paralyzing muscles that control arms, legs, trunk, speech, swallowing and breathing, leaving the intellect undamaged.

A few live many years with it--physicist Stephen Hawking, author of “A Brief History of Time,” is the best-known example, having been found to have the disease in 1963--but the average length of the illness is three to five years until death.

In 5% to 10% of cases, ALS runs in families. Last year, researchers at Massachusetts General tracked the gene involved to chromosome 21, and they are very close to identifying the gene itself.

Last summer, there was more promising news: Scientists at Johns Hopkins Medical Center said they had found that the brains of people with ALS were unable to get rid of glutamate, a chemical that excites nerve cells to action. Too much glutamate, some researchers suspect, kills the motor neurons. There is some evidence that blocking excessive buildup of glutamate, a complex task, might save these nerve cells.

The most hotly pursued research work on the disease concerns the growth factors.

Hope has arisen from work done on mice with ALS-like symptoms. The animals were injected with ciliary neurotrophic growth factor, or CNTF, a substance the body produces in response to peripheral nerve damage. The treated mice had less severe symptoms than those who didn’t receive the drug.

Test-tube studies were equally encouraging: Motor neurons that were expected to die immediately lived for days.

Similar studies in animals of IGF, or insulin-like growth factor, suggest it can also stave off motor neuron death and even induce sprouting, or growth, of neurons.

But the only way to find out if these drugs will work in people is to enter hundreds of fatally ill patients in drug trials and play a kind of roulette. Some patients will get the drug; others will take a placebo. Patients and doctors will not know who is taking what. This kind of study--called a double-blind placebo-controlled study--is considered the most efficient way to test a drug’s effectiveness.

Most of the 56 research centers already have chosen patients for the trial--people mildly to moderately ill whose disease is progressing at a trotter’s pace--and are awaiting the FDA nod.

For many ALS patients, hope remains strong.

Sarah Bookbinder, at 74 an avid walker, musician and traveler, learned two years ago that she had ALS.

After picking out her coffin and arranging her funeral, the former history teacher enrolled in a drug study at Columbia Presbyterian Hospital. She continues to take deprenyl, a medication used to treat Parkinson’s disease that some thought would help in ALS. But that study and others recently showed it doesn’t work. She says that she will take it anyway until her doctor says otherwise.

“I don’t have time to die,” she says. “I have too much to do.” Bookbinder, frustrated that she can no longer button a coat or walk to the mailbox, refuses to give up. “People must have hope,” she said. “For now, there’s not much else.”