The New York Times: “A Deadly Disease of Infants Attracts New Research Money,” by Anahad O’Connor
When Ellen Goldstein of Brooklyn gave birth last November to her only child, Owen, medical tests offered no clues that five months later he would be crippled by a deadly and irreversible genetic disease.
Tests shortly before Owen was born revealed no abnormalities, and a physical evaluation right after his birth showed he was in perfect health.
So when Owen, once a lively and playful baby, began showing signs of low muscle tone and lost the ability to move his left arm only two months into his life, doctors were mystified.
“We noticed his right wrist was drooping, so we started investigating,” Ms. Goldstein said. “We went to an orthopedist and found out he was missing some of his reflexes.”
At 5 months, Owen lagged behind other children his age in muscular skills, like lifting his head, and his doctors concluded that he had a disorder known as spinal muscular atrophy. Ms. Goldstein and her husband, Hamilton Cain, learned that the disease would leave Owen paralyzed for his life, which doctors predicted would last no more than about two years.
With no cure or medical treatment for the disease, doctors could offer little more than palliative care to Owen, who has a rare mutation of the disease. “There’s really no therapy to reverse the course of this,” said Dr. Charles Schleien, Owen’s pediatrician at Children’s Hospital of New York-Presbyterian. “We just try to make the children comfortable and decide whether to place them on ventilators as their muscles get weaker.”
The disease strikes about 1 in 6,000 newborn Americans each year, roughly the prevalence of amyotrophic lateral sclerosis, or Lou Gehrig’s disease, a better known neuromuscular disorder.
Yet research on spinal muscular atrophy, the leading genetic killer of infants and toddlers, has not, over the years, been financed as heavily as Lou Gehrig’s disease and other genetic disorders, said Dr. Darryl De Vivo, director of the Spinal Muscular Atrophy Clinic at Columbia-Presbyterian Center of New York-Presbyterian Hospital.
“I don’t like to pit one disease against another, but it’s relatively common in our population and should get better funding,” Dr. De Vivo said. “Until three or four years ago, there was less than $1 million devoted to it. Last year, for instance, A.L.S. had about $30 million and cystic fibrosis got $117 million.”
Diseases that have a celebrity face, like Michael J. Fox with Parkinson’s or Lou Gehrig and Dr. Stephen J. Hawking in the case of A.L.S., can attract attention and government financing, some advocates say.
The disease Owen has kills more than half of its victims in childhood, leaving few celebrities to promote the search for a cure.
“When we went to Capitol Hill, a lot of senators asked `Do you have a celebrity?’ ” said Loren Eng, who runs a foundation for spinal muscular atrophy and has a daughter with a milder form of it. “It’s a real fact that when a celebrity goes to the Hill to testify, they get a packed room — unlike when the parent of a dying child goes to testify.”
For all of those reasons, some scientists say, efforts to find a cure have been strained, even though the cause of the disease is well understood and a possible treatment is in sight.
Spinal muscular atrophy, which is often likened to a genetic form of polio, is caused by a wasting away of nerve cells in the spinal cord. The wasting leads to increasing muscular weakness, an inability to walk or stand and, in many cases, death. Those with the most severe form, like Owen, can end up with collapsed lungs, kept alive only by a breathing device.
Parents almost never see the disease coming because no state requires prenatal screening for it, Dr. De Vivo said. And in some severe cases, like Owen’s, the genetic mutation that causes it is so rare that there is no test for it.
For years, this genetic disease was poorly understood and might have been underdiagnosed because so many victims died young. But a breakthrough came in 1995 when researchers in France identified a gene, called survivor motor neuron that is necessary for motor neurons to function normally. Its absence may set off the disease.
In addition to the gene, most people have several copies of a backup gene, known as S.M.N. 2 that produces a much smaller amount of the protein that S.M.N. 1 generates. Nearly every person with spinal muscular atrophy has a mutated S.M.N. 1 gene, but it is the number of S.M.N. 2 genes — the backup — that determines the severity of the disorder.
Dr. De Vivo noted that a person with a defective S.M.N. 1 gene but four or more S.M.N. 2 genes would have the less severe form of the disease, called Type III. Such patients, despite difficulty, might still be able to walk and stand alone.
At the other end of the spectrum, Dr. De Vivo said, a patient with only one or two backup genes to compensate for the mutated S.M.N. 1 gene would have Type I spinal muscular atrophy. In such cases, muscles deteriorate, breathing becomes a battle, and death is almost certain before the age of 2.
The more copies of S.M.N. 2 mean a greater chance of survival. For Dr. De Vivo and other doctors anticipating a treatment for the disease, the implications are obvious: find a drug that can trick S.M.N. 2 into ramping up its output.
Indeed, the probability of finding a treatment or cure appears strong enough to scientists at the National Institutes of Health that they are giving the disease special consideration. Usually, experts sift through a mountain of proposals and determine where the institutes’ financing should go. In departing from this practice, however, the institutes have decided to direct money toward S.M.A. research and are now soliciting proposals from researchers to investigate a treatment.
“S.M.A. not only has the kind of frequency and severity to warrant more research, but there are really good opportunities for developing a treatment,” said Dr. Kenneth H. Fischbeck, chief of the neurogenetics branch at the National Institute of Neurological Disorders and Stroke. “It seems to be a good target, so our institute is taking kind of an experimental approach to funding.”
If the new approach to financing research hastens the discovery of a treatment, “it can serve as a model for other hereditary forms of neurodegenerative diseases like muscular dystrophy and Huntington’s disease,” he added.
Several studies aimed at manipulating the S.M.N. 2 gene are under way in the United States and Europe, Dr. Fischbeck said, but getting a drug on the market may take more than a decade.
To cut that time, some scientists are looking at drugs that have already been approved by the Food and Drug Administration for other diseases. This year, for example, scientists in Germany and at the health institutes showed that valproic acid, an epilepsy drug, could more than double S.M.N. protein levels in cell cultures taken from spinal muscular atrophy patients.
But the drug must still go through several years of clinical trials to determine whether is is safe and effective for patients with spinal muscular atrophy, Dr. Fischbeck said. In the meantime, the researchers are trying to step up efforts, in the hope that pharmaceutical companies might take an interest in developing a drug.
“It takes a push from government and foundation-sponsored research to get to the point where a treatment is imminent enough that a biotech company might decide the disease is worth their while,” Dr. Fischbeck said. “There’s a gap, and we’re trying to build a bridge to cover it.”