Getting to the heart of Alzheimer's disease

A leading group of Alzheimer's disease researchers led by Dr Chris Eckman at the Mayo Clinic in Jacksonville, Florida have found that an enzyme normally associated with the cardiovascular system, endothelin converting enzyme (ECE), may be able to hit Alzheimer's disease at its very core.

Over 35% of 85 year-olds suffer some sort of dementia, Alzheimer's disease being the most common. It is predicted that by 2025, 22 million people will fall victim to this devastating disease.

A leading group of Alzheimer's disease researchers led by Dr Chris Eckman at the Mayo Clinic in Jacksonville, Florida have found that an enzyme normally associated with the cardiovascular system, endothelin converting enzyme (ECE), may be able to hit Alzheimer's disease at its very core.

In the latter part of the last century, following studies on patients with Down's disease and a familial form of Alzheimer's disease it became generally accepted that a protein, beta-amyloid 42 likely played a crucial role in the development of both of these diseases as well as the more common late onset Alzheimer's disease.

Beta-amyloid 42 accumulates in the plaques which characterize Alzheimer's disease. This accumulation causes the gradual death of neurons in the hippocampus and the cortex advancing the devastating symptoms of this disease.

Unfortunately as is often the case, the availability of pharmaceutical treatments has lagged behind the advancement of science and most treatments of Alzheimer's disease are still targeted to reducing various symptoms or maximizing the efficiency of the diminishing number of nerve fibers.

According to a DiscoveryDossier published this week by the drug development consultants, LeadDiscovery, Dr Eckman's work may soon change this situation.

Dr Eckman reasoned that an extremely effective way of slowing the progress of Alzheimer' disease may be to remove beta-amyloid 42 as it is being produced. It was found in a series of groundbreaking experiments that ECE was able to do just this.

Crucially, it was found that by forcing cells to produce higher levels of ECE-1a or ECE-1b, up to 90% less beta-amyloid 42 accumulated outside the cells. A similar effect could be obtained by adding a fragment of this enzyme to cells producing beta-amyloid 42. This suggested that increasing naturally occurring levels of ECE or boosting the efficiency of this enzyme could remove beta-amyloid 42 from the brain delaying the development of Alzheimer's disease.

One risk of this approach is that since ECE is an important regulator of the cardiovascular system, treatments could be associated with serious side effects. This does not however appear to be the case since mice geneticaly engineered to produce high levels of ECE were completely healthy.

According to LeadDiscovery consultants "This particular strategy offers a novel way of targeting Alzheimer's disease. Most drugs in development or on the market act to preserve neurotransmission or to dampen the behavioral changes associated with this devastating disease. To our knowledge this is one of the first instances that removal of beta-amyloid 42 has been shown to be possible. This is truly exciting. Of course treatments remain a long way off. Dr Eckman must first find a way of raising the levels of ECE in the brain or stimulating its activity. Difficult, yes, but we believe that with Dr Eckman's expertise in both Alzheimer's disease itself and in developing tools able to very rapidly screen for candidate drugs success should be possible ".

Of course industrial involvement would expedite this process, and having patented the approach Dr Eckman is now looking for partners to exploit his breakthroughs.

As a final note, it is becoming evident that reducing beta-amyloid 42 at the same time as targeting neurotransmission may bring about dramatic effects. In other words drugs emerging from Dr Eckman's lab are little to be the perfect partner to many of the other drugs already available.

For information on in-depth analyses of this and related work visit the LeadDiscovery website at http://www.leaddiscovery.co.uk/target-discovery/discoverydossiers.html

LeadDiscovery is a leading Sussex based firm of drug discovery, development and commercialization consultants whose aim is to combine a background in the pharmaceutical industry with an internet platform to help academic and biotech based research groups to exploit their technology.