05/05/2010 05:12 am ET | Updated Nov 17, 2011

Alzheimer's Drug: Dimebon Is Down The Drain

The pharmaceutical company Pfizer announced today that its investigational Alzheimer's medication, Dimebon, has failed an important test of its effectiveness in the treatment of Alzheimer's Dementia. A great deal of hope and expectation had been placed in this medication. Its apparent failure has been a disappointment not only for Pfizer, but for many physicians and sufferers of Alzheimer's Dementia that were expecting Dimebon to be a breakthrough in the treatment of the illness.

Results came from an FDA approved Phase III clinical trial named CONNECTION that was being run by Pfizer and its subsidiary company, Medivation. Phase III refers to a specific stage in the clinical investigation of new medications for human use. After animal studies have shown a medication to have promise, Phase I trials establish doses and safety of the medication in human beings. Phase II trials then try the medication on small groups of patients to see if the drug shows effectiveness and safety in its use in humans. Phase III trials start after all indications are that the medication is safe and likely to have benefit for patients. Phase III trials involve large numbers of patients in several different clinics or medical centers, and their results are safeguarded by the use of placebos and so-called double blind designs that prevent both the patient and the doctor from knowing who is getting what until the results are determined.

The CONNECTION trial has been a Phase III study looking at the effects of Dimebon in about 600 patients with mild-to-moderate AD in North America, Europe, and South America. The patients in the study had an average age of 74.4 years, and met criteria for the diagnosis of Alzheimer's Dementia of mild to moderate severity. The patients were randomly assigned to receive either Dimebon or a placebo, i.e., "sugar pill" for six months. During that time their cognitive function was regularly assessed to determine what if any changes were occurring, or if the two treatment groups differed from one another. The finding was that after six months, those patients receiving Dimebon were not at all different from those who merely received the placebo. In other words, the Phase III trial showed that Dimebon was no more effective than a sugar pill. It offered no benefits for patients suffering mild to moderate degree of Alzheimer's Dementia.

The finding of the apparent ineffectiveness of Dimebon was surprising and disappointing largely because a 2008 clinical trial published in the prestigious journal The Lancet had obtained such positive results with the medication. In that study, 183 patients with mild to moderate Alzheimer's Dementia appeared to greatly benefit from treatment with Dimebon. I have noted comments in the press that this earlier study was suspect because it was performed in Russian clinics. However, the study was performed as a collaboration of the Russian Academy of Sciences with groups from Baylor, Mount Sinai, UC San Diego, and Georgetown University Colleges of Medicine. Moreover, as I have suggested, the study met the impeccable publication standards of The Lancet. Those remarkable first results with Dimebon were also consistent with what had been learned in animal studies about the effects of this drug on the brain. Dimebon has been found to mimic effects of both of the classes of drugs currently FDA approved to treat Alzheimer's Disease. That is, it blocks abnormal activity at NMDA receptors in the brain, as does the FDA approved memantine, and it blocks the enzymatic breakdown of the chemical messenger acetylcholine in the same fashion as drugs such as Aricept. In addition, Dimebon may help prevent build up of abnormal tau protein, which causes the neurofibrillary tangles of Alzheimer's. There are also reports that it can block some of the neurotoxic effects of amyloid, the abnormal protein that accumulates in the brains of sufferers of Alzheimer's.

Even before any trials in human beings, Dimebon had been found to improve the cognitive function of rats genetically engineered to exhibit changes in the brain and behavior similar to those seen in humans with Alzheimer's Dementia. Thus, there were compelling reasons to predict that Dimebon would again be shown to be helpful in improving the cognitive function of patients with Alzheimer's. Sadly, this was not the case.

Some explanation may be found as to why Dimebon may work in some but not other patients with Alzheimer's Dementia. Moreover, studies are ongoing to see if Dimebon may yet be helpful as an add on to currently approved medications for Alzheimer's Dementia. Nonetheless, it is now clear that Dimebon is not a miracle cure-all. To quote the great biologist, Thomas Huxely, "A beautiful theory has been destroyed by an ugly fact."

The quest for medications that can improve the cognitive function of sufferers of Alzheimer's dementia continues. It is possible that something will be found to stop or even reverse the degenerative processes of the illness. However, at present the most effective medications only slow the progression of the illness. Some people inherit genes that make it likely they will develop Alzheimer's Dementia no matter what they do. Thankfully, this is a small minority of people. For most of us, the best approach to Alzheimer's continues to be to avoid the illness by proper diet, stress reduction, sleeping well, staying active mentally, physically and socially, and by using vitamins, herbs and nutraceuticals that can slow down the neurodegenerative processes that cause damage to the brain. It is important that these steps be initiated in your 40's and 50's, when this damage to the brain tends to begin.