Scientists studying brain-wasting diseases linked to mad cow have warned that a new class of cancer drugs have the potential to set off similar brain deterioration.

The new cancer-treatment compounds, known as proteasome inhibitors, block cell machinery used to digest unwanted proteins. But the researchers, led by Susan Lindquist, a professor at the Massachusetts Institute of Technology, said using such compounds in mice helped produce brain-wasting symptoms.

Drugs in the class include Velcade, which is being tested in patients by Millennium Pharmaceuticals, Cambridge, Mass., and the National Cancer Institute. David Schenkein, vice president for clinical oncology at Millennium Pharmaceuticals, said the findings weren't viewed as cause for concern because the drug isn't able to cross into the brain.

[Karl Note:  You can be certain that some adverse publicity on a drug under development by some drug company will be met with denials of applicability by the company. You can also be hopefully sure that a vigorous core of media journalists will sniff out these negative reports to keep the public informed -- the drug companies will certainly NOT publicize these reports -- but will hide them if they can.]

Millennium's is the only proteasome-inhibitor cancer drug to enter human tests, said John Wright, a senior clinical investigator at the National Cancer Institute. The federal cancer institute said it had 28 studies with the drug ongoing in different types of cancer.

After learning of the possible risk, the NCI held several meetings during the summer with experts in prion disease and from the Food and Drug Administration, said Louise Grochow, a senior manager at the National Cancer Institute. Dr. Grochow said the risk was deemed small, and that no significant changes would be made to the design of the studies. However, she added that the NCI would require more thorough neurological evaluation of patients. "So far, there is no evidence that the risk is being played out," said Dr. Grochow.

Proteasome inhibitors aren't the same as protease inhibitors, drugs that are used widely to treat HIV infection and AIDS.

Dr. Lindquist and co-workers found the proteasome effect while studying the molecular basis of prion diseases, which include mad cow and variants that affect humans and deer.

The diseases have been linked to misshapen prion proteins, which accumulate around nerve cells killed off by the condition. However, Dr. Lindquist reports Friday in the journal Science that normal prion proteins were able to cause nerve degeneration when they were present inside a cell's liquidy interior, or cytoplasm.

The proteins were able to accumulate after the scientists applied proteasome-blocking chemicals to the cells. The proteasome is the cellular machinery that normally digests proteins.

The cause of the brain disease has been a major scientific question, and Dr. Lindquist said her paper suggested a possible explanation, though conclusive proof was lacking. Jiyan Ma of Ohio State University, who carried out much of the work, said it could be that one form of the prion protein causes the symptoms, while another form lets it pass between animals. "We think the transmission and the toxicity are separate," said Dr. Ma.

Write to Antonio Regalado at antonio.regalado@wsj.com²

Updated October 18, 2002 12:48 a.m. EDT

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