I spent last week in Lebanon at a conference organized by Saint George Hospital and the University of Balamand. In Lebanon approximately 60% of the population are muslim and the rest christian. While I was there I had the opportunity to visit Byblos, the oldest city in the world dating back over 7,000 years to the times of the ancient phoenicians.  It is now dominated by a Crusader Castle. The first written language came from Byblos and thus it gave its name to the Bible. I also got to see the magnificent Cedars of Lebanon,  which were used to build King Solomon’s temple.

At the conference, Professor Bruno Vellas, from Toulouse in France, talked about the development of drugs for Alzheimer’s disease. He pointed out that the effects of the drugs available at the moment to treat the disease are not overly dramatic. According to him there are over 70 drugs under development for this devastating condition.

 Many of the drugs focus on altering the production of amyloid-beta protein. Beta-amyloid in high concentrations inhibits memory, produces damage to nerve cells and is deposited as toxic clumps in the brain. A number of drugs that alter the enzymes that cut the amyloid-beta out of a larger protein are being developed. These are called anti-secretases.  Unfortunately the first of these, called Flurizan, developed by Myriad Pharmaceuticals, had disappointing  clinical outcomes. Another set of drugs are attempting to stop the beta-amyloid from forming insoluble sheets in the brain. These are called anti-aggregants.  The vaccine studies that produced antibodies to block the effect of beta-amyloid proved to be somewhat toxic. Others are making antibodies to beta-amyloid in  the laboratory, and then giving them to humans.

 My group has developed a small molecule that blocks the production of the precursor for beta-amyloid. This molecule is called an antisense, as it blocks the ability of the message from the DNA (messenger RNA) to tell the cell to produce the protein. our animal studies have been very successful showing that it improves memory, stops oxidative damage to the brain and improves clearanceof the beta-amyloid out of the brain. It also had a positive effect in Down’s Syndrome animals. We have formed a small biotech company, called Edunn Biotechnology, to try to take the drug into clinical trials. Edunn is the Norse godess who brought apples to the Norse gods thus keeping them eternally young. I need to confess that I have a conflict of interest regarding how good I believe it will be. 

Since 1983, dimebon has been used as an antihistamine in Russia.  A recent study in patients in Russia suggested that dimebon may help persons with moderate dementia. Pfizer is conducting the CONCERT trial to see if they can obtain FDA approval. it has many effects including altering the function of a number of small molecules in the brain that carry messages from one nerve cell to another. These molecules have been shown to have effects on  memory. It also blocks the nerve damaging effects of beta-amloid and may alter function of the mitochondria in cells. The effect on the mitochondria may prevent cell death.

A century-old drug, methylene blue, also alters mitochondrial function. A study in England suggested it may also work in humans to improve memory in persons with Alzheimer’s disease. Studies in animals by Dr Susan Farr, at the St Louis Veterans Administration, have found that alpha-lipoic acid, which prevents free radical damage, enhances memory in an animal model of Alzheimer’s disease.

Both insulin and beta-amyloid are broken down in the brain by the same enzyme, called insulin degrading enzyme. Studies are underway to see if drugs that improve the function of insulin, will improve memory in Alzheimer’s Disease.  

Numerous other drugs are under-development in the attempt to cure this terrible disease. For those interested in volunteering studies they can find further information about available studies from Saint Louis University (314-268 5385), the Alzheimer Disease Research Center at Washington University or the St Louis Alzheimer’s Disease Association.