CP-690,550: Pfizer's New Drug To Suppress Immune System (animal studies)

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New Drug To Suppress Immune System

December 29, 2003

http://www.intelihealth.com/IH/ihtIH/EMIHC271/333/21291/373763.html?d=dmtICNNews

(NIH) -- Immunosuppressant drugs are designed to inhibit the body's

immune system so that your body doesn't reject transplanted organs, and

to treat autoimmune diseases such as lupus, rheumatoid arthritis, eczema

and psoriasis-conditions in which the body's own immune system attacks

healthy, normal tissue as if it were an invading microbe.

Unfortunately, current immunosuppressants can cause serious side effects

such as diabetes, elevated cholesterol and high blood pressure. A new

drug, developed by Pfizer Global Research and Development with help from

NIH's National Institute of Arthritis and Musculoskeletal and Skin

Diseases (NIAMS), has now been successfully tested in mice and monkeys,

and may eventually prove to be a major help for those needing organ

transplants or with autoimmune diseases.

The new drug is designed to inhibit an enzyme called JAK3, a protein

discovered by the NIAMS team in 1994 that is found only in immune system

cells. Current immunosuppressants target enzymes found in cells

throughout the body, resulting in toxic side effects. In setting out to

find a compound that selectively inhibited JAK3 so that it only affected

immune cells, Pfizer researchers searched through a library of chemical

compounds developed by the company. They eventually arrived at a

compound they call CP-690,550.

They tested CP-690,550 in mice with heart transplants and in monkeys

with kidney transplants. In both cases, the animals treated with

CP-690,550 survived much longer than untreated animals. Their survival

was also longer than that of animals treated with other

immunosuppressant drugs in past studies, with fewer side effects.

This finding culminates a long process of research and discovery by the

NIAMS team. After discovering JAK3, the team demonstrated that this

protein, called a kinase, was critical for the cell signaling process,

resulting in the development of infection-fighting white blood cells.

They went on to show that the mutation of the gene encoding JAK3 was

responsible for a form of severe combined immunodeficiency (SCID).

Because JAK3 is essential for immune cell function, and because its

expression is limited to blood cells, the team proposed that inhibiting

JAK3 might be the basis for a new class of immunosuppressant drugs. The

group then entered into a collaborative research and development

agreement with Pfizer-a partnership that has facilitated Pfizer's

development of this new drug.

This study shows that inhibiting JAK3 has the effect of suppressing the

immune system, while not affecting other systems of the body. Further

animal studies are now being done to determine if this drug could be

tested safely in humans. If it proves safe and effective, it would prove

a major advance in the development of immunosupressant drugs.