LABORATORY TEST SUGGESTS POSSIBLE DEMENTIA TREATMENT

A study published in Science (April 20) showed that in a laboratory test, rat brain cells were injured by very small amounts of gp120, a protein made by the AIDS virus. The cells could be protected by small concentrations (100 nM) of nimodipine, a prescription drug used to reduce neurological damage in certain cases of bleeding in the brain. The concentrations effective in the laboratory test can be attained in patients.

In the laboratory study, gp120 appeared to harm nerve cells by causing them to absorb too much calcium -- over 30 times the normal level. That is why nimodipine, a calcium channel blocker, was tried in this test-tube study. The authors suggested more research to see if this drug might be useful in treating or preventing AIDS-related dementia or other neurological damage.

What Happens Next?

Results from a laboratory study of rat brain cells cannot predict what will happen in patients. Even if the drug could work, no one knows the right dose. While nimodipine is fairly safe in its standard use (the most common side effect is decreased blood pressure), there is no information on its use by persons with AIDS, or on combining the drug with AZT or other treatments which would still be necessary, since nimodipine would have no effect on the HIV infection itself.

AIDS TREATMENT NEWS called the senior researcher of this study, Stuart A. Lipton, M. D., a neurologist at Children's Hospital in Boston and at Harvard Medical School. He told us that he has a clinical trial ready to go; he is now talking with Miles Pharmaceutical, the company which owns the drug, seeking support for it. We mentioned that other funding might be found, but Dr. Lipton feels strongly that the company which owns the drug should pay for the study.

We called Miles Pharmaceutical and reached a spokesman in the public relations office. He said that while Miles was ready to support pre-clinical and animal studies (he emphasized those words in our conversation), they wanted more information before trying it in patients -- for example, a test with another animal model. He mentioned that Miles had no experience with AIDS, but had been told that rats do not get the disease; scientific implications of that fact might be considered.

Comment

It became clear that here was another example of the kind of misunderstanding that repeatedly derails practical AIDS research, due to the lack of national leadership ready to move in an emergency. It is understandable that a pharmaceutical company unfamiliar with AIDS would want more than a study of rat cells in a laboratory dish before sponsoring a trial. And yet the drug is believed safe, and ultimately -- no matter how much animal work is done -- the only way to see if it works will be for patients to try it. Dr. Lipton wants a trial now so that people will not start using the drug on the basis of one laboratory study, in the absence of any human trial for its use in treating AIDS-related neurological damage. We sensed that the parties had been talking to each other for some time before the article was published; they seemed to have reached an impasse.

Since no one knows if the drug will work at all for AIDS-related dementia or other neurological problems, no one knows if it would only be preventive, or if it could reverse symptoms already present. Fortunately AZT can often reverse dementia, showing that the damage is not irreparable. If nimodipine can clearly improve patients' condition, then a clinical trial would be relatively easy; it could be conducted by a community-based trials organization, or by an individual physician. But if the drug could only prevent the problem and had to be given in advance, a clinical trial would be difficult to administer, because it would require many patients and a long time to obtain the required evidence.

If no trial happens soon -- we especially need the easy trial, for treatment as opposed to prevention -- it is inevitable that people will start trying the drug without waiting for a scientific study.