Two research groups have determined the three-dimensionalstructure of the protein that binds to the immunosuppressantdrugs FK506 and rapamycin, a finding that could lead to betterdrugs for autoimmune diseases and to fight organ transplantrejection.

Identification of the drugs' binding site in the FK506 bindingprotein (FKBP) is a first step in the so-called rational design ofdrugs that are more effective and have fewer side effects thanthose currently used.

Harvard University scientists report in today's Science thatthey used nuclear magnetic resonance (NMR) spectroscopy todetermine the structure of FKBP. The Harvard team, withresearchers from Cornell University, also report the X-raystructure of the complex between FKBP and FK506.

Cambridge, Mass.-based Vertex Pharmaceuticals Inc.announced Thursday that its NMR structure of FKBP willappear in the May 16 issue of Nature.

FK506, which prevents activation of T cells (white blood cellsthat mount an immune response), may be administered topatients prior to an organ transplant. Rapamycin, which blocksgrowth factors from promoting T cell growth, may be used totreat chronic immune response disorders.

Fujisawa's FK506, now in clinical trials, is up to 1,000 times aspotent as Sandoz's cyclosporin, which holds a two-thirds shareof the $600 million worldwide immunosuppressant drugmarket. However, both drugs have side effects, includingkidney damage, said Vertex scientist Dr. Matthew Harding.


Harvard Medical School researchers have used geneticallyengineered herpes simplex virus-1 (geHSV-1) to destroyglioma brain tumor cells implanted in mice.

The approach relies on geHSV-1's ability to replicate anddestroy actively dividing cells. The virus does not attack non-growing cells, including normal brain cells.

Glioblastomas, which represent 29 percent of primary braintumors, attack 5,000 people each year in the United States. Theaverage survival rate is less than a year.

The researchers report in today's Science that injection ofgeHSV-1 into tumors implanted under the skin or in the brainsof nude mice destroyed tumor cells. Two of seven mice withtumors in the brain that were injected with a high dose ofgeHSV-1 lived at least 19 weeks and showed no evidence oftumor cells. Mice receiving no geHSV-1 died within sevenweeks.

The authors propose further engineering the virus to be certainit only attacks brain tumor cells. -- CTV

-- Carol Talkington Verser, Ph.D. Special to BioWorld

(c) 1997 American Health Consultants. All rights reserved.