Hopes and Setbacks in Alzheimers

The degeneration of patients with Alzheimer’s Disease is a tragic progression, robbing those that love them of the very essence of the personality they knew. And to this day there is no effective treatment for the disease, with a handful of drugs in use to slow down the progression. But there is no halting it – not yet.

One of the major difficulties is one of early diagnosis: by the time people realize there is a problem, the disease is already quite advanced. It is all too easy to overlook little lapses of memory and much more desirable to believe they are nothing important. Most of the time, they really are nothing – until they are not.

Some research from Duke University has given some optimism that there may be a more reliable way to predict whether someone is likely to suffer from the disease. Dr. Allen Roses had previously discovered that patients with a gene called ApoE4 that have an unusually large chance of developing Alzheimer’s, although no one had yet been able to find an effective treatment that capitalizes on this finding. Furthermore, it did not explain why patients with the more common ApoE3 gene also developed the disease. His more recent finding looks at a gene associated with the ApoE gene called TOMM40 and that there were characteristics of that gene that tallied with the progression of Alzheimer’s. The group at Duke is cautioning that this is a preliminary finding that needs to be duplicated in other laboratories. But if it is true then it will be an exciting and fruitful area of research.

This good news was welcome because another highly anticipated study gave only bad news. Glaxo’s diabetes drug Avandia failed to show any effectiveness in a clinical study. The loss of a potential $300 million for Glaxo was in itself bad news for them, but it is a setback for the theory that Alzheimer’s is a form of diabetes in the brain. This theory has had several successful studies outside of the clinic, but the Avandia study was the first to put it to the test with patients, where it was hoped that it would be able to regulate blood sugar levels in the brain, just as it does in the blood of diabetic patients. However, though the study was safe, it did not show the desired effect, adding only a few points to the cognitive scores and most effective in patients that did not carry the ApoE4 gene that is so strongly linked to the disease.

Clearly, it is not the end of this approach. There are many subtle reasons that Avandia might not have succeeded, from insufficient drug crossing the blood-brain barrier to a difference in the way that sugar is regulated in the brain. (Avandia works differently to many diabetes treatments by helping the insulin in the body to work more efficiently). It is unfortunate that it did not show at least some effect to give the other related compounds hope though, at a time that companies will be weighing the risk and benefit of funding expensive clinical studies.

At least some compounds will continue to be studied. One example comes from the Mount Sinai School of Medicine, who have studied the cognitive effect of a diabetic treatment called NIC5-15. The company manufacturing the compound, Humanetics, sponsored the study and there is an interview with their CEO here.

It is clear there is still a difficult road ahead for companies hoping to treat this terrible affliction, but the growing need for an effective treatment is a excellent stimulant to innovation and that the research is now getting at the heart of the problem has to be seen as an encouraging sign.

Update: In the Pipeline blogged on this subject, looking at the failure to show efficacy by a number of compounds.

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