Will modified curcumin help with Alzheimer's disease?
Curcumin-based drug slows down the progression of Alzheimer's disease
LifeSciencesToday based on Salk News: Salk scientists develop drug that slows Alzheimer's in mice
A short course of treatment with a compound developed by scientists at the Salk Institute for Biological Studies, known as J147, restores memory and slows down the progression of Alzheimer's disease in old mice. The results of preclinical trials of this compound, just published in the journal Alzheimer's Research and Therapy (Prior et al., The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer's disease mice), may pave the way for the creation of a new drug for the treatment of Alzheimer's disease.
"J147 is an amazing new compound, because by slowing the progression of the disease and reversing the symptoms of memory impairment after a short course, it really has a good prospect of becoming a therapeutic drug for the treatment of Alzheimer's disease," says study leader Marguerite Prior, a researcher at the laboratory of Cellular Neurobiology at the Salk Institute.
Despite years of research, there are no drugs that can influence the development of Alzheimer's disease. To date, FDA-approved drugs, including Aricept, Razadine and Exelon, are able to provide only a short-term improvement in the condition of patients and have nothing to do with slowing down the steadily progressive irreversible extinction of their cognitive abilities.
According to the Alzheimer's Association, more than 5 million people in the United States suffer from Alzheimer's disease. This disease is the sixth leading cause of death in the country and the only one among the top 10 on the list that cannot be prevented, cured or at least slowed down.
Compound J147 was obtained by the laboratory of Professor of Cellular Neurobiology David Schubert. Schubert and his colleagues have moved away from the prevailing trend in the pharmaceutical industry to search for targets for drugs in biological pathways involved in the formation of amyloid plaques – aggregates of abnormal protein characteristic of Alzheimer's disease. Instead, they developed a number of new synthetic compounds (based on natural substances of plant origin, in particular, curcumin) and tested their effectiveness in protecting cells from several pathological processes associated with brain aging on live, laboratory-grown neurons. Based on the results of testing each modification of the leading chemical compound, they managed to change their chemical structure, making the effect much more powerful.
(Fig. sandiegobiotechnology.com )
"The study of Alzheimer's disease has traditionally focused on one target – the amyloid pathway," Professor Schubert notes, "but, unfortunately, clinical trials of drugs developed on this basis have failed. Our approach is based on the pathology associated with aging – the main risk factor for the development of Alzheimer's disease and other neurodegenerative diseases – and not on the features of this disease."
To test the effectiveness of J147 in much tougher preclinical trials, Professor Schubert and his colleagues conducted experiments on mice with a disease model more closely corresponding to the symptomatic stage of Alzheimer's disease in humans (obviously, compared to the one the article about which was published a year and a half ago; the then press release of the Salk Institute almost literally coincides with the text current – VM).
As a result, in 20-month-old genetically modified mice with severe Alzheimer's pathology, the administration of J147 with food for three months restored the ability to remember and led to a decrease in the level of soluble amyloid and increased levels of neurotrophic factors important for memory.
In another experiment, scientists compared the effectiveness of J147 and Arisept, the most widely prescribed drug for Alzheimer's disease, and concluded that in a number of memory tests, mice receiving J147 showed better or similar results.
"Not to mention obtaining an extremely promising therapeutic agent, both the strategy of using mice with an already developed disease and the process of developing drugs based on aging make this study interesting and exciting," says Professor Schubert, "since this is closer to what is happening in the human body, which at the time of diagnosis and the beginning of treatment has already developed a gross pathology." In most studies, drugs are tested that are designed to be prescribed before the manifestation of pronounced symptoms of the disease. These are preventive rather than therapeutic means, and perhaps this is the reason that everything ends with animal testing.
Compound J147 affects several cellular processes associated with the pathology of Alzheimer's disease, including the level of brain-derived neurotrophic factor (BDNF), a protein that protects neurons from damage by toxins and stimulates the growth of new neurons and their communication with other brain cells, as well as participating in the memorization process. Postmortem analysis of the brain tissue of patients with Alzheimer's disease indicates a reduced level of this protein.
According to scientists, having such a wide range of neuroprotective properties, J147 may prove to be an effective treatment for other neurodegenerative diseases, such as Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis, as well as stroke, although in their studies the effectiveness of this compound as a treatment for these diseases has not been directly studied.
According to the researchers, compound J147, which has the ability to improve memory, along with a safe and patient-friendly oral form of administration, may become an "ideal candidate" for clinical trials, the search for funding sources is already underway.
Portal "Eternal youth" http://vechnayamolodost.ru
15.05.2013