Hopes are revived for CJD drug

October 26, 2002 New Scientist by Charles Choi

A DRUG that helped four patients with Creutzfeldt-Jakob disease for a short time has revived hopes of a treatment for the fatal brain disease -- if doctors can prevent it damaging the liver and accumulating in the brain.

The former anti-malarial drug quinacrine was first tried as a treatment for vCJD, the human form of mad cow disease, last year. It seemed to cause a dramatic recovery in British patient Rachel Forber. But she stopped taking the drug after liver complications, and died last December. The new study carried out by scientists at Fukuoka and Kyushu universities in Japan, was presented at the American Neurological Association meeting last week. It involved three patients with sporadic CJD, which develops spontaneously, and one who caught the disease from an infected tissue transplant.

Patients were given 300 milligrams of quinacrine daily through a feeding tube (because of swallowing difficulties). Within a few days they started smiling and making eye contact when spoken to, and one regained some speech. Another patient, who previously couldn't sit up, was able to stand up and walk with help.

But there was a price to pay. The patients' skin turned yellow, and tests showed their livers were malfunctioning. They all relapsed after one to two months. Neurologist Masashi Nakajima, who led the study, suggested this was due to quinacrine accumulating in the brain.

He says the findings showed at least some CJD brain damage could be reversed. "Quinacrine might prove to be the treatment of choice," he says. "Maybe by lowering dose levels after the first two weeks, we can avoid toxicity."

Nakajima also says that low-dose quinacrine might help those at risk of developing CJD: for example, where a biopsy shows evidence of CJD prion proteins in people without symptoms.

How these findings relate to people with vCJD is unclear, and quinacrine's side effects are an obvious drawback. But it's the only drug shown to work against any form of CJD.

So far 127 people, mainly from Britain, have contracted vCJD. But the idea that thousands more may have caught the disease from BSE-infected beef is driving research.

After news broke of Rachel Forber's remission, the British government said it would carry out human trials of quinacrine. But it hasn't yet. A spokesman for the Medical Research Council, which is organising the research, says: "The trial design is still being peer-reviewed. These things can take quite a time."

Britain's Department of Health is also investigating pentosan polysulphate, a chemical sometimes used to treat cystitis, as an alternative CJD treatment. The drug hasn't yet been tested on people with CJD, but it is known to reduce infection rates in mice exposed to scrapie, the prion brain disease that affects sheep.

The Japanese scientists also recently announced that pentosan polysulphate, infused directly into the brains of scrapie-infected mice, increased survival rates even when given late in the course of the disease. They plan to test this on CJD patients in future.

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