Will buffer solution cure Alzheimer's disease?

Vyacheslav Golovanov, GeekTimes based on LiveScience: Novel Chemical 'Washes Away' Alzheimer's Plaque in Mice 

A group of Korean scientists from several institutes involved in neuromedicine and brain research have discovered a chemical that eliminates the symptoms of Alzheimer's disease and improves cognitive abilities in mice. The substance was given to mice by simply dissolving it in water.

The drug that had such an amazing effect on the mammalian brain is a fairly well–known compound EPPS (or HEPPS – 3-[4-(2-Hydroxyethyl)-1-piperazinyl]propanesulfonic acid). In biochemistry and biology, it is used as a buffer solution that preserves acidity when added to a mixture of acids or bases.

Science has not yet established the causes and course of Alzheimer's disease. Symptoms of the disease are a disorder of short-term memory, impaired speech and cognitive functions. It is only known that about 1% of cases of diseases occur for genetic reasons. Alzheimer's disease is the most common cause of dementia.

The key feature of the disease is the accumulation of amyloid plaques and neurofibrillary tangles in brain tissues. So far, scientists fighting the disease are able in some cases to stop the formation of new protein plaques – but it has not yet been possible to wash out existing plaques from the brain.

The Koreans discovered that EPPS somehow attach to plaques and break them into smaller molecules. In addition, the substance manages to overcome the hemato-encephalic barrier. It is a physiological barrier or filter between the circulatory system and the central nervous system found in all vertebrates. It protects the nervous tissue from microorganisms circulating in the blood, toxins, and unwanted contacts with cells of the immune system. The small size of the EPPS molecules allows the substance to overcome this barrier, and therefore it can be taken even by simply dissolving in water.

No side effects have yet been detected in mice taking EPPS. Doses ranging from 30 to 100 mg per kilogram of weight successfully coped with the crushing of plaques, while doses of up to 2000 mg per kg of weight did not harm mice in any way. Of course, it is necessary to conduct separate studies on humans, including on the toxicity of the drug. 

Article by Hye Yun Kim et al. EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by segregation of amyloid-β oligomers and plaques is published in open access in the journal Nature Communications.

"When treating chronic diseases such as Alzheimer's disease, it is always better to aim to reduce the dose of medication as much as possible," explains Yun Soo Kim [YoungSoo Kim]. "Considering that people may have to take the medicine for the rest of their lives, it is necessary to check it for safety."

Since the nature of the disease has not yet been identified, scientists are even arguing about whether amyloid plaques are the cause or consequence of the disease. Korean biologists have found that after the active destruction of plaques in mice, learning abilities increase and memory improves. In this regard, they conclude that plaques are the direct cause of the symptoms of the disease.

John Hardy, an Alzheimer's disease specialist who recently received an award for the discovery of a genetic mechanism that promotes the formation of amyloid plaques, commented on the work of Korean scientists: "It must be remembered that behavioral disorders in humans are caused by the loss of nerve cells, which does not occur in mouse models of the disease. Therefore, improving the cognitive abilities of mice does not necessarily mean that this will happen in humans."

He also notes that people will have to take a medicine that cleaves plaques in large doses. Kim, in turn, points out that the accumulation of plaques in patients begins 10-15 years before people begin to demonstrate cognitive function disorders. During this time, they have every opportunity to prevent such a fate.

A month earlier, American biologists reported successes in the fight against the accumulation of toxins in the brain that destroy blood vessels. They received the substance J147, which not only improved cognitive abilities, but also demonstrated an improvement in the state of the brain, similar to rejuvenation. However, again, experiments have so far been conducted only on mice.

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22.12.2015