Friday, July 18, 2008

Dimebon Improves All 5 Alzheimer's Measures

183 Russian Alzheimer's patients were studied for a year to compare the safety and efficacy of Dimebon, an obscure antihistamine that is not on the market anywhere in the world. The study was conducted by Baylor College of Medicine researchers, and published in the Lancet.
In the study, the authors noted that Dimebon is the first drug for Alzheimer's disease that demonstrated continued improvement in patients over a 12 month period. Other approved drugs do not have this effect.

Half of the 183 patients in the Russian study received Dimebon; the other half were given a placebo or an inactive pill. Clinicians at the study sites then monitored the patients' progress over the next year on five different outcomes. All of those in the study had mild to moderate Alzheimer's disease.

"What we saw in the clinical trial is that people on the medication continued to improve over time," Doody said. "Those on placebo continued to decline."

Researchers believe the medication works by stabilizing mitochondria, the cellular components that produce energy, and possibly by inhibiting brain cell death. Researchers evaluated patients' thinking and memory ability, overall function, psychiatric and behavioral symptoms, and ability to perform daily activities.

"Usually at this point in a drug's development, we are happy to see improvement in one of the outcome measures," Doody said. "We saw improvement in all five." _SD
The study was reportedly well-designed and conducted. The significant and ongoing improvement of the drug group over the placebo group for at least a year, is quite impressive. Rights for the drug are owned by Medivation, Inc. (Nasdaq: MDVN), which has enjoyed a recent boost in stock price.

More information on this study and other new research on Alzheimer's Disease at WaPo:.
The study was done in Russia because dimebon had been approved there as an antihistamine. Dimebon is made by the San Francisco-based biopharmaceutical company Medivation. Doody is on the Scientific and Clinical Advisory Board of Medivation and has stock options in the company.

Another phase III trial has just started, Doody said. This six-month trial is being conducted in the United States, Europe and South America and is now in the process of recruiting several hundred patients, she noted.

"We are anxiously awaiting the completion of the next study, so that we can see if this drug could potentially be approved for treating Alzheimer's patients," Doody said.

Gandy said the drug does appear to be superior to the currently approved medicines for Alzheimer's.

"This is the first new promising symptomatic therapy in a long time," Gandy said. "This drug could potentially add to the effects of other drugs such as Aricept, Namenda and Exelon," he said. "I think it's a pretty exciting development."

Partially excerpted from a previous posting at Al Fin

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Friday, July 04, 2008

Methionine Restriction and QOD Feeding

The latest issue of Rejuvenation Research contains some articles dealing with dietary restriction strategies for extending lifespan.
The latest issue of Rejuvenation Research is online. You'll find a few more esoteric items on calorie restriction biochemistry, but one paper on methionine restriction is more accessible and interesting. By way of a reminder, recall that there's a fairly good argument for the beneficial effects of calorie restriction to largely stem from lowering the intake of methionine, one of the eight essential amino acids in your diet.

On Methionine Restriction, Suppression of Mitochondrial Dysfunction and Aging

Rats and mice, when subjected to methionine restriction (MetR), may live longer with beneficial changes to their mitochondria. Most explanations of these observations have centered on MetR somehow suppressing the effects of oxygen free radicals.

The other paper that caught my attention is a nice demonstration that the benefits of calorie restriction don't necessarily have anything to do with insulin-like growth factor 1, IGF-1. For those who have been following research into IGF-1 metabolism and aging, a field with at least as much interest as investigations into mitochondria and aging, that might be a counterintuitive result.

Effect of Every Other Day Feeding on Mitochondrial Free Radical Production and Oxidative Stress in Mouse Liver

It is known that dietary restriction (DR) increases maximum longevity in rodents, but the mechanisms involved remain unknown. Among the possible mechanisms, several lines of evidence support the idea that decreases in mitochondrial oxidative stress and in insulin signaling are involved but it is not known if they are interconnected.

It has been reported that when C57BL/6 mice are maintained on an every other day (EOD) feeding their overall food intake is only slightly decreased and plasma insulin-like growth factor (IGF)-1 is even somewhat increased. In spite of this, their maximum longevity is increased, analogously to what occurs in classic DR. Thus, this model dissociates the increase in longevity from the decrease in IGF-1 observed in classic DR.


These results support the possibility that EOD DR increases maximum life span at least in part through decreases in mitochondrial oxidative stress which are independent from insulin/IGF-1-like signaling.

Various manipulations of diets in animal models should provide us with more information about aging mechanisms, as research designs become more sophisticated to tease out effective manipulations, and as collection and analysis of animal response data delves more deeply into the actual molecular mechanisms that are altered.

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