Wednesday, November 29, 2006

Amyloid-busting compound to start trials in Alzheimer’s





By Mike Nagle

28/11/2006 - US drug developer Samaritan Pharmaceuticals has filed a patent for a new drug that could treat a wide range of neurodegenerative disorders, including Alzheimer’s disease, by clearing out amyloid plaques in the brain.

The compound, called caprospinol (SP 233), is remarkable because it appears to not only block the formation of amyloid, thought to contribute to the nerve damage seen in Alzheimers patients, but also cause deposits already present in the brain to disappear.
Alzheimer's is an incurable, progressive brain disorder that causes dementia. Current treatments work to slow down the progress of the disease by boosting neurotransmitter levels in neurons, but it has not been possible to reverse any damage already done by the disease. Experimental strategies to treat the disease include gene therapy but as yet, are not employed clinically. Therefore, there is a pressing need for the development of new treatments.

The managing director of Samaritan Pharmaceuticals, Europe, Dr Christos Dakas, told DrugResearcher.com that aside from its potential in Alzheimer's, disease, ”our scientists believe that it [SP-233] could be effective in any disease that involves neurodegeneration. But it is not something we'll be pursuing at this stage.”

Other neurodegenerative diseases include Huntington disease, multiple sclerosis and Parkinson's disease.

The main constituent of amyloid plaques, amyloid-beta protein, accumulates at abnormal levels in the brain of Alzheimer's sufferers. The protein is toxic to mitochondria found in cells and ultimately causes nerve cell death. This in turn, causes the symptoms of the disease, including loss of memory, an inability to learn, make judgments and perform day-to-day tasks. Caprospinol has been developed to protect mitochondria functions against the effects of amyloid-beta. It does this by binding to amyloid-beta and preventing it entering neurons.

Dr Dakas said: “We are in the process of initialising a Phase I maximum dose and safety study.”

The study should be completed in the first quarter of 2007 and Dr Dakas hopes that if everything continues to progress well, the drug could be available in two to three years.

He added: “We have three more products in development in the Alzhemier's disease program. At this stage, SP-233 is the most advanced.”

Several other drugs designed to taget amyloid formation are in development. US Pharmaceutical company Elan, in collaboration with Wyeth, New Jersey, have developed a drug aimed at inducing an immune resonse designed to clear beta amyloid. The drug, ACC-001 is currently in Phase I clinical trials.

Frence based ExonHit Therapeutics are developing a drug that reduces amyloid plaque build-up through the production of a related blood protein. EHT 0202 has completed a Phase I clinical trial and is currently being assessed in Phase Ib trials.

A further study has shown that a drug previously approved for treatment of several immune disorders can also benefit patients with mild to moderate Alzheimer's. Weill Medical College of Cornell University, New York, have demonstrated that Intravenous Immunoglobulin (IVIg), a purified mixture of human antibodies, can be used to remove amyloid plaques from the brain. The antibiotics also appear to block the toxic effects of amyloid-beta.