Taking Matters--and Science--Into Their Own Hands
Late last year, eight patients with a fatal neurological disorder gathered in Newton, Mass., with their loved ones and a handful of scientists for a crash course: ALS 101.
Their goal: to learn everything they could about amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease.
Their instructor was Jamie Heywood, a 34-year-old engineer turned teacher, scientist and pharmaceutical entrepreneur who, in 1998, took his own course when his brother Stephen was diagnosed.
Heywood quit his job at a neuroscience think tank in California and headed home to Massachusetts to take care of his brother. He’s now taken on the task of finding a cure for the disease, which strips away the body’s motor neurons and leaves its victims trapped inside their bodies. A progressive paralysis takes hold, and patients die within an average of five years of diagnosis, when the motor neurons that guide respiration give out.
“The thing about Jamie,” says Stephen, “is that he can be very focused, but not for a long period of time.” But as Stephen Heywood’s disease has progressed, his older brother’s determination has not lost its fire. His efforts remain focused on trying to produce treatments for the 30,000 people diagnosed with ALS--a disease with no known cure.
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The Heywoods are a new breed of patient advocates: people who want to speed the science along by raising money that allows researchers to pursue ideas that might not qualify for scarce federal funding. These brothers have gone a step further: They started the ALS Therapy Development Foundation and hired scientists to carry out the studies.
The brothers, supported by their parents, are collaborating on a project called FDA 2000, a plan developed by Harvard’s Dr. Steve Gullans to test all 1,500 drugs approved by the U.S. Food and Drug Administration to see if any can work against ALS. This is the first time scientists have taken such an approach.
The goal is a shortcut to an effective ALS drug; the development of new compounds can take more than a decade. So Jamie Heywood became executive director of the foundation and began, in effect, to build a pharmaceutical company from the outside in: hire the scientists, design the studies, stock up on mice. “This is definitely the way to go,” he said.
And he knows he’s racing against time. “We can now screen thousands of drugs and play it backward. Anything that is promising in mice becomes stunningly important as a candidate in human ALS.”
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Heywood and his staff--including six scientists--work closely with Gullans, a scientist who turned his attention to ALS when a relative was diagnosed. It was Gullans who proposed the radical approach of “opening the medicine cabinet and testing every drug.”
Gullans is funded in his new career by Heywood’s organization and Project ALS, another research and advocacy group started by the Estess sisters of New York City, one of whom has ALS. Gullans is hoping that medicines already in the pipeline could have an impact not just on ALS but also on other neurological disorders.
The first round of tests targeted neuronal cells primed to die a death similar to ALS motor neurons. (Motor neurons themselves are too finicky to use in testing.) The scientists identified about 30 promising drugs. Further testing found that eight of the 30 were potent enough to warrant more tests.
That’s where Jamie Heywood comes in. He hired the scientists and opened two laboratories in Boston, where hundreds of mice engineered to develop ALS are going to be tested with Gullans’ “hit list” of drugs.
Gullans said it is too early to release the names of the medicines.
Already, research data suggest that a massive inflammatory system attack occurs in the diseased motor neurons. Scientists who have analyzed spinal cord tissue from ALS patients have found the same thing: reactive astrocytes and microglia, evidence of an inflammatory process. Gullans and others now believe there is a powerful inflammatory component that could be driving the motor neurons--the cells that crowd the spinal cord and receive messages from the brain that coordinate movement--to death.
When Heywood set out to find a cure for ALS, what he read was discouraging. Many medicines had been tried, all unsuccessfully. Then he read about glutamate transporter protein, which seemed to be missing in the spinal tissue of ALS patients. He called Dr. Jeffrey Rothstein, an ALS researcher at Johns Hopkins Medical Institutes whose work on the gene that produces the glutamate transporter protein convinced Heywood that gene therapy to repair the glutamate transporter system was a potential cure for his brother. An animal study suggested that the concept would work.
With Rothstein’s paper in hand, Heywood called Dr. Matthew During, the director of the Gene Therapy Center at Jefferson Medical College in Philadelphia. Years earlier, During had conducted gene therapy trials on newborns with Canavan’s disease, a fatal neurogenerative disorder that causes damage to the brain’s white matter. The geneticist worked with Heywood and Rothstein to devise a study, and the trial was approved by Jefferson Medical College’s Institutional Review Board. But it wound up on hold after Jesse Gelsinger, a teenager with a rare metabolic disorder, died in September 1999 in a gene therapy experiment just miles from During’s lab, at the University of Pennsylvania.
Stem cell therapy has shown promise in a number of neurological disorders. Rothstein has pursued stem cells’ role in ALS, setting sights on placing them in the environment of the spine to replace the lost motor neurons. Even if these newly dividing cells only nourished the patient’s existing motor neurons with enriching growth factors, scientists say, it could slow the disease process and extend the lives of patients.
In addition, During and his colleagues are working on vaccines to protect the motor neurons from succumbing to the disease.
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At the ALS 101 course, Stephen talked to fellow patients about some of the medicines he’s been taking. He’d been involved in an experimental drug trial of BDNF, or brain-derived growth factor, supported by Amgen Pharmaceuticals. He tried a Chinese herb, one of the substances that protected the neurons from dying in a test-tube, but the tar-like substance tasted awful and had to be consumed three times a day. He’s taking an anti-inflammatory COX-2 inhibitor as well as creatine, which has been shown in animals to protect the motor neurons. He added Prozac, shown in studies to have neuroprotective effects.
These days, Jamie Heywood sounds more like a scientist than an engineer. He and During have written a scientific paper and have submitted it to a medical journal. Gullans and Heywood are getting the FDA 2000 list in shape to go online in the next few months. The list will include information about each of the medicines and supporting data, Heywood says.
Stephen Heywood says it is hard to say which treatments work and which don’t. Today, two years after his diagnosis, he spends most of his time in a wheelchair, a trained carpenter directing from the sidelines. He’s gotten married and had a son. He continues to help his brother run the foundation, whose Web site is at https://www.als-tdf.org.
Jamie Heywood thinks that he has already made a difference in his brother’s life. Stephen agrees. “My brother thinks big. What he has done doesn’t surprise me. If there’s an answer, he’ll find it.”
