Alzheimer's: from a taurine-like molecule the hope for a new drug
Alzheimer's disease: possibly a new drug from a taurine-like molecule
It comes from a small molecule similar to Taurine, the amino acid found in some energy drinks, the hypothesis of developing a treatment that can fight Alzheimer's. In fact, the substance, called EPPS, may destroy in laboratory mice amyloid plaques, the typical accumulations of protein that form in the brain during the early stages of the disease, destroying neurons.
This is the discovery made by Korean researchers at the Korea Institute of Science and Technology in Seoul, and published in the world's leading scientific journal Nature.
Alzheimer's disease: causes and symptoms
Alzheimer's disease is the most common form of dementia: it affects about 5 percent of people over 60 years of age and, in Italy, an estimated 500,000 sufferers. Alzheimer's is caused by an alteration in brain function that results in a range of difficulties for the patient in conducting normal activities of everyday life. The disease affects areas of the brain involved in the processing of thought, memory and language, and other mental functions, causing progressive amnesia, states of confusion, personality changes, loss of control of bodily functions, mood changes, and spatial-temporal disorientation.
At the biological level, the typical signs of the disease are observable in the brain only after the patient's death and are the presence of "amyloid plaques," clusters formed mainly by a protein called β-amyloid, and that of fiber tangles (neurofibrillary clusters), as well as the loss of connections between neurons. Along with genetic predisposition, other factors such as diet and lifestyle may also play a role in the onset of the disease.
More and more studies are showing that, as with other diseases, following a proper diet by combating diabetes, obesity and inflammation can reduce the risk of Alzheimer's disease. In this regard, omega-3 fatty acids, particularly DHA, which is a key component of neuron membranes, appear to have a protective function against Alzheimer's(read here). Unfortunately, there are no drugs that can stop and reverse the disease, and all available treatments aim to reduce symptoms.
EPPS destroys amyloid plaques
In the course of their research, Korean scientists treated lab rats with EPPS (or 4-(2-hydroxyethyl)-1- propanosulfonic piperazine), a substance very similar to Taurine found in energy drinks, that had genetic mutations necessary to "mimic" Alzheimer's disease and its symptoms. After only 3 months of treatment, the animals showed improvements in learning and reduction of amyloid plaques in the brain.
According to the scientists, the observed recovery of cognitive abilities was facilitated by the fact that these mice are unlikely to develop brain atrophy, whereas, unfortunately, when a patient is diagnosed with the disease, the nerve tissue shows both amyloid plaques and atrophy. In any case, the results obtained have suggested the development of EPPS-based therapies capable of slowing down brain degeneration, especially in the early stage of Azheimer's. Future drugs are unlikely, therefore, to make patients regain lost nerve tissue, but they will be able to halt the progression of the disease and reduce mortality.
Something more about the study
During the experiments that led to the discovery, the Korean researchers added EPPS, a substance used in the laboratory to regulate the acidity of solutions during experiments, to the drinking water given to experimental mice. The animals, thanks to the insertion of two genes, exhibited some symptoms of Alzheimer's, including memory deficits and reduced ability to perform activities such as swimming or passing through small mazes. The scientists gave the mice several daily doses of EPPS, up to 30 milligrams (per kilogram of animal weight) for three months.
After this treatment, by repeating learning and memory tests, the animals had shown a strong improvement in performance, which had become comparable to that of normal mice. Analysis of brain tissue had also shown, in those treated with EPPS, a significant decrease in amyloid plaques. In particular, mice that had received the 30-mg dose had lost almost all plaques present in the hippocampus, the region of the brain implicated in memory processing. In contrast, untreated mice showed a doubling of the number of plaques in the hippocampus during the same time period.
The action of EPPS appears to be due to its ability to cross the blood-brain barrier, the structure that surrounds the brain by protecting it, due to its small size, and then "break" amyloid plaques without causing any side effects, in doses between 30 and 100 milligrams per day. Administered in larger amounts (up to 2,000 milligrams per kilogram of animal), however, the molecule showed toxic effects; it is clear, therefore, that many tests will have to be carried out to determine the safe doses relative to administrations for humans.
The benefits of EPPS
According to Dr. Kim, one of the authors of the research, the findings finally pave the way for future therapies that target the direct destruction of amyloid plaques to halt the progression of the disease. Compared with other molecules studied, EPPS is very cheap to produce, and is a molecule already available in the chemical market, and, compared with drugs or antibodies that require injections, it can be easily administered orally.
In humans, it usually takes about 10-15 years from the accumulation of amyloid plaques to brain atrophy and the onset of cognitive deficits. The efficiency of EPPS-derived drugs will therefore be a powerful therapeutic tool, especially in the early stages of the disease and when early diagnosis for Alzheimer's is finally available.
Sources: Hye Yun Kim, Hyunjin Vincent Kim, Seonmi Jo, C. Justin Lee, Seon Young Choi, Dong Jin Kim& YoungSoo Kim."EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques." Nature Communications.
