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Genetically Engineered Drug Uses Diphtheria Poison to Relieve Arthritis

May 6, 1991

BOSTON (AP) _ Doctors say they fused a natural human protein with diphtheria poison to create a medicine that can dramatically relieve the pain and swelling of severe rheumatoid arthritis.

″It’s really remarkable pain control. One lady went dancing. One woman said she felt like Cinderella,″ said Dr. K. Lea Sewell.

Testing is still in the preliminary stages, but doctors said virtually all symptoms of the disabling disease were eliminated in about one-quarter of those who had the treatment.

The treatment, interleukin-2 fusion toxin, is produced by Seragen Inc. of Hopkinton. It is being tested elsewhere for use against some forms of blood cancer.

Dr. David Trentham, who also worked on the study, said the treatment has the most potential of any arthritis drug developed since the benefits of methotrexate were recognized about five years ago.

In testing at Boston’s Beth Israel Hospital, 13 patients with severe arthritis took injections of the new drug daily for a week. Four showed dramatic improvement, while eight others had at least some response.

″Three of them felt like they did not have arthritis,″ Sewell said.

Among the patients was a woman who suffered from 20 swollen joints and two hours of stiffness each morning. After the treatment, her only symptom was one swollen joint in an index finger.

″I think this agent has a lot of potential,″ commented Dr. C. Frederick LeMaistre of the University of Texas at San Antonio, who is using the hybrid protein to treat lymphoma and leukemia.

He said the treatment is designed to target only those cells that are active in the disease, and thus avoids damaging the immune system.

Some 7 million people have rheumatoid arthritis, one of the two most common forms of arthritis, according to the Arthritis Foundation.

The treatment is a product of genetic engineering that welds diphtheria toxin to a protein that seeks out a variety of white blood cells that in arthritis mistakenly destroy the lining of the joints.

The diphtheria-armed protein zeros in on these blood cells, enters them and eventually kills them.

″It’s not a rerun. It’s a new category of medication,″ said Sewell.

Sewell outlined the results Sunday at a meeting in Seattle of the American Society for Clinical Investigation. The approach was developed by Dr. Jack Murphy of Boston University.

Beth Israel is the only hospital using the treatment for rheumatoid arthritis.

None of those in the current study were helped by methotrexate, a cancer medicine that can cause a variety of unwanted side effects.

Sewell said the fusion protein’s symptoms included mild nausea and low fever. Patients felt improvement during the first week or two of therapy, and the benefits lasted one to four months.

Rheumatoid arthritis results from a foul-up in the body’s defenses against disease. White cells called activated T cells ordinarily patrol the body in search of microbes and cancer. But in a case of mistaken identity, they attack the linings of the joints and destroy them.

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