Minocycline, an antibiotic being tested as a possible treatment for a variety of neurodegenerative diseases, may actually cause harm, a group of U.S. scientists has warned.

The scientists reported that in a clinical trial of patients with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, those who received the drug minocycline declined more rapidly than those who received a placebo.

Their report, published Thursday in the journal Lancet Neurology, comes just a week after the Multiple Sclerosis Society of Canada announced it was funding a multi-centre Phase 3 trial to look at whether the inexpensive and off-patent minocycline can slow the progression of MS when treatment is started in the earliest stages of the disease.

One of the lead researchers in the MS study, Dr. Wee Yong of the University of Calgary, admitted the U.S. findings gave him pause when he heard them presented in April at a meeting of the American Academy of Neurology.

But Yong said he thinks the trial should proceed. "We will of course be cautious," Yong said in an interview. "We are always cautious in a clinical trial. But we don't really want to kill anything too early because of what is observed in another context which may not have any bearing to the current condition that we're trying to treat."

"I should point out that we are dealing with different diseases altogether. The pathology or the reason for ALS is very much different from the pathophysiology of MS."

The U.S. researchers were studying minocycline as a possible therapy for ALS, a progressive and eventually fatal degeneration of motor neurons that destroys the brain's ability to instruct the body to move.

The study was led out of Columbia University Medical Center in New York, but involved investigators from medical institutions across the United States.

Early tests positive

Testing in mice genetically engineered to suffer from ALS showed the drug was beneficial. Likewise, early testing in humans — the small Phase 1 and 2 trials designed to establish safety and look for early signs of effectiveness — were sufficiently positive to allow the researchers to proceed to a larger and more expensive Phase 3 trial.

But there, to their surprise, they discovered that people taking the drug declined and died more rapidly than people who received a placebo.

"We were shocked. We were just absolutely stunned when we saw these results," one of the lead investigators, Dr. Robert Miller, said from San Francisco, where he is director of the Forbes Norris ALS Research Center at California Pacific Medical Center Research Institute.

"That was our first thought. But our second thought was that we need to get these results out because we need to avoid this happening to other people with other diseases."

Miller and his co-authors acknowledge in their article that their animal model might have been faulty, or they might have been using too high a dose of the drug.

But they also cautioned researchers who are studying minocycline as a potential therapy for conditions such as Parkinson's and Huntington's diseases, stroke and MS to take note of their results.

"The justification for these trials should be reassessed in light of our findings: Minocycline might have a detrimental effect on patients with neurological diseases other than ALS," they wrote.

Yong and his colleagues have also conducted animal studies and Phase 1 and 2 clinical trials in humans and have seen nothing that suggests minocycline would be harmful in MS patients.