Lawrence D. Jacobs, Pioneer In Fight Against Ms

BUFFALO, N.Y. -- Lawrence D. Jacobs, M.D., credits his involvement with the treatment and prevention of multiple sclerosis -- the interest that has become his life's work -- to serendipity.

A native of Buffalo, Jacobs graduated from Niagara University and earned his medical degree from St. Louis University. He joined the University at Buffalo faculty in 1973 as a clinical assistant professor of neurology after completing an internship, residency and fellowship in neurology at Mt. Sinai Hospital and School of Medicine in New York City, where he also was a junior faculty member. In the early years of his career, Jacobs' research interests were neurologic-based eye disorders and CT scanning of brain lesions of various origins.

In Buffalo, Jacobs was affiliated early on with Roswell Park Cancer Institute as a consultant, where he developed a professional relationship with Arnold Freeman, M.D., and several other scientists conducting the earliest clinical trials of interferon as a possible cancer treatment. The drug became available to Jacobs for neurologic research because of his close relationship with those scientists.

"We asked ourselves: 'What are the neurologic diseases of viral and dysimmune etiologies that might be appropriate for trials of interferon therapy?'" Jacobs noted. "We first considered Lou Gehrig's Disease, but ultimately we decided on MS because Buffalo happens to be in a geographic region where MS occurs with high frequency and there were so many patients in Western New York with MS. It was just luck."

Supported by local funding from the Baird Foundation, Delaware North and UB, Jacobs began his research. His preliminary results, published in Science in 1981, reported that interferon injected into the spinal fluid appeared to stop or reduce MS flare-ups. This led to another, larger multicenter double-blinded study that was supported in part by a grant from the National Institutes of Health (NIH) as well as the Baird Foundation and

other local sources. The positive results of that trial, confirming those of the earlier study, were published in Lancet in 1986.

By then, Jacobs had the NIH's full attention. But in order to secure funding for an even larger multicenter definitive trial, he knew he had to show there was a possibility the drug could slow the accumulation of physical disability naturally associated with untreated MS, in addition to reducing the number of flare-ups.

MS affects 250,000 to 300,000 people in the U.S., with 200 new patients diagnosed per week. It is a progressive neurological disease in which the body loses the ability to transmit messages among nerve cells, leading to loss of muscle control, paralysis and, in some cases, death. For reasons that are not fully understood, people who live between the 38th and 52nd north latitudes on the globe are particularly susceptible to the disease. Western New York is located at about the 43rd north latitude.

Jacobs was able to put together a research proposal that satisfied the NIH requirement regarding disability, and in 1990 he received $4.5 million over four years to conduct a large study of interferon's effectiveness in slowing or reversing the accumulation of physical disability in MS patients.

"Biogen then came in to support the Phase III trial expenses, as well as the cost of the interferon," Jacobs said. "We developed a wonderful relationship over the years."

The company provided substantial monetary support and a supply of genetically engineered interferon called recombinant interferon beta-1a, identical to the naturally occurring molecule in humans, to complete the Phase III trial, a final trial required to prove the drug safe and effective. Results showed the drug significantly slowed the progression of disability, significantly decreased the relapse rate, and significantly reduced the number of MS-related brain lesions, compared with patients who were untreated (placebo group) during the trial.

Avonex®, Biogen's brand name for the drug, was approved by the FDA in 1996. It now is being used by about 35,000 patients in the U.S. and another 9,000 in Europe, Jacobs said, and is currently being introduced in Canada with other markets to follow.

Jacobs currently is the principal investigator for a $12 million, 50-center study being conducted in the U.S. and Canada of the potential efficacy of Avonex® in preventing the development of clinical multiple sclerosis in patients who are at high-risk for the disease, such as those with optic neuritis.