Paradoxical Results for Alzheimer’s Drug
Posted by SR in News, tags: alzheimer's, dimebon
Although not without opponents – and still unproven – the theory that reducing levels of β-amyloid peptides will lessen neuronal damage and cognitive deficits remains a central tenet of Alzheimer’s disease research and the focus of many pharmaceutical companies. Last week, however, it was reported at the Alzheimer’s Association annual meeting in Vienna that Dimebon® (latrepirdine), a drug which has shown clinical benefit in people with mild to moderate Alzheimer’s disease, increases levels of β-amyloid in the releasate from isolated nerve terminals and in the interstitial fluid from the brains of transgenic mice bred to model Alzheimer’s disease. This unexpected result raises questions about how Dimebon® works and also, perhaps, about the validity of the ‘amyloid hypothesis’. One possibility is that the neuroprotective effects of Dimebon® are sufficient to outweigh the adverse effects of increased concentrations of β-amyloid. Preclinical studies have suggested that Dimebon® could prevent neuronal damage and dysfunction by stabilising or improving mitochondrial function. In addition, biochemical studies have shown effects on α-adrenergic receptors, histamine receptors and serotonin receptors as well as on Ca2+ flux and apoptosis. Alternatively, Dimebon® could cause an acute increase in amyloid levels, but lower levels on chronic dosing, or it could play a role in amyloid transport. Whatever the explanation for the present results, further investigations into the mechanism of action of Dimebon® and the relevance of animal models of acute amyloid lowering to human disease are of key importance.
Dimebon®, which has been used in Russia to treat hayfever since the 1980s, is being jointly developed by Medivation and Pfizer and is currently in phase III clinical trials.
Related posts:
- Hayfever Drug Shows Promise for Treatment of Alzheimer’s Disease A study published in the July 18th issue of The Lancet shows that a drug once used in Russia to...
- Nicotinic α-7 Receptors in Alzheimer’s Disease – On or Off? A number of groups are developing nicotinic α-7 receptor agonists or partial agonists for the treatment of Alzheimer’s disease. It...
- GPCR Target for Alzheimer’s Disease Available treatments for Alzheimer’s disease offer relatively small symptomatic benefits and more effective treatments are much needed. β-Amyloid has been...
- Prion Protein linked to Alzheimer’s Disease Mis-folded prion proteins have been linked to a number of neurological diseases including scrapie in sheep, bovine spongiform encephalopathy (BSE,...
- How ApoE4 May Increase Alzheimer’s Risk ApoE is a lipid transport protein with roles in transport of dietary lipids, regulation of plasma cholesterol, and protection from...
Related posts brought to you by Yet Another Related Posts Plugin.
This entry was posted on Wednesday, July 22nd, 2009 at 8:30 am and is filed under News. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.
Entries (RSS)
Several people now think that they need to go back to the bench and rethink the “amyloid cascade hypothesis” from the beginning. There may be complex and unexpected aspects of amyloid at work or the cause may lie with some other factor like Tau. An article in Nature a couple of months back succinctly captured the frustration after the failure of two large-scale clinical trials and talked about possible future directions.
http://www.nature.com/news/2008/081112/pdf/456161a.pdf
Any research that provides additional insight into Alzheimer’s is critical to finding a cure. It’s also important for patients and families affected by Alzheimer’s to consider participating in clinical studies. Another study to consider is the ICARA Study, whose goal is to explore if an investigational drug, called Bapineuzumab, can help slow the progression of Alzheimer’s Disease. Patients and families affected by Alzheimer’s can visit http://www.icarastudy.com to see if they might be eligible to enroll.