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Researchers are working on new compounds against Alzheimer's

again, not a must-have announce two pharmaceutical companies, a drug against Alzheimer's disease fulfilled the hopes. Last week, Roche and AC Immune announced that two studies with a total of 1500 patients will not be continued. The tested drug Crenezumab showed no improvements in the patients. "We are very disappointed," says Andreas Monsch. The Memory Clinic, the Monsch at the University age medicine of the Felix-Platter-Spital directs in Basel, was involved with a few patients in the study.

Such messages are, for some years, the rule when it comes to new Alzheimer's drugs. Numerous studies with more than 100 substances have failed. The goal for the researchers since a few years is nothing less than the cause of the disease and to treat for the first time, not only the symptoms but the nerves die and the progressive Forget to stop.

most of these agents target a Protein fragment that clumps together in the brains of Alzheimer's patients and in characteristic Plaques deposited, the so-called Beta-Amyloid (strategy A). Researchers and pharmaceutical companies see this piece as a suitable point of attack, has a long history. An example: Although Alzheimer's disease due to age occurs in about 95 percent of the cases, from about the age of 60. Years of age,. Very rarely, however, can bequeath families, the sick nerve will die. All of the previously discovered genetic mutations in these families mean that more Beta-Amyloid, or such that the lumps are increased and deposited.

"We do not know the exact mechanism of how Alzheimer's disease ."Andreas Monsch, head of the Memory Clinic at the Felix-Platter-Spital in Basel

at the beginning of the 2000s, researchers almost euphoric, as it was able to develop antibodies against Beta-Amyloid. The substances should fish the harmful fragments from the brain. Some antibodies have shown that they can remove Beta-Amyloid, but the course of the disease could stop them, no substance, and certainly not the patient, her thinking ability.

112 substances in studies

"in the Meantime, you have to ask yourself whether Beta-Amyloid actually not so relevant in the course of the disease, as previously thought," said Monsch. Currently, some of the studies in which other active ingredients may prove whether it is worthwhile, Beta-Amyloid attack. Monsch appreciates the opportunities that show positive results, on the "50 to 50".

The great Confidence that in the medium term, to succeed, to fight the cause of the disease, but it is gone. The experts are today in agreement: "We do not know the exact mechanism of how Alzheimer's disease develops," said Monsch.

His US-colleague, Jeffrey Cummings agreed with him. However, the Alzheimer's expert from the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas is optimistic. Cummings followed, together with colleagues, for years, meticulously, of what substances are in the Pipeline of pharmaceutical companies and how you in various studies have a cut off. The Team has summarized last year in an Overview of all the studies that are listed in the state Register of the United States (clinicaltrials.gov). The scientists have published data in the journal "Alzheimer's & Dementia". The studies with the drug Crenezumab from Roche and AC Immune are included.

image to enlarge

Therefore, were used a year ago, 112 substances in human testing. Of which 26 are in Phase 3 studies, i.e., an average of 860 patients, 63 substances in Phase-2 studies with 150 participants and 23 in the first compatibility studies with up to 12 volunteers. Conclusion: There are some important studies with new agents to run currently, and it more substances are added. So the positive message.

"but We have also learned from failed studies a lot," says Cummings. Therefore, he believes that the approach to combat Beta-Amyloid, for done. He was "very excited" that in currently ongoing studies, at least six new substances directed against a different molecule, called Tau (strategy B). Thus, some new approaches focus on another disease feature in the brains of Alzheimer's patients. The Protein Tau stabilizes in the nerve cell skeleton, the so-called micro-tubules. If Tau are modified proteins are pathological, they can be stored in the nerve cell. The so-called neuro-fibrils are bundles of damaging the cell, and the microtubules become unstable. The nerve cell dies, and the released Tau-aggregates infect other nerve cells.

"The more Tau deposits are found in the brain, the stronger the memory are failures," says Cummings. The Tau-pathology is however not specific for Alzheimer's disease – it also occurs in Parkinson's disease and other forms of dementia. Therefore, researchers accepted that they could not be the main cause of Alzheimer's disease.

well-Known dye in the Test

"The first Phase 3 trial with an Anti-Tau drug, however, failed also recently," says Cummings. The active ingredient, which should prevent the Aggregation of Tau, is methylene blue, a well-known dye that has been used for the treatment of Malaria. But also with methylene blue and other Anti-Tau compounds, more studies will follow.

A different approach to the inflammatory processes in the brain, where the microglia cells are involved, which function as immune cells. Cummings could imagine that it once for a very early stage of Alzheimer's disease might be useful medicines against Beta-Amyloid. Preparations against Tau and inflammatory processes could be used, as soon as the first symptoms such as forgetfulness.

The American scientists appealed but also to the pharmaceutical companies continue to develop drugs that combat the symptoms of Alzheimer's disease. So far, there are only a handful of substances with only two mechanisms of action (strategy C). It's been 15 years since the last preparation for the treatment of Alzheimer's disease was admitted – "the world," says Cummings; it was the memantine.

researchers and patients need a lot of patience

this year, could add another. A substance with the cumbersome name of GV-971 in the approval process in China is currently going through. The company Green Valley Pharmaceutical from Shanghai has presented at the end of last year, the results of a successful pivotal study of 818 patients at a Congress in Barcelona. Therefore, the compound could slow the mental decline, at least during the 36 – week study period. Where is the substance, often a sugar, attaches, however, in the brain, not know the developer. Project Manager, Meiyu Geng from Shanghai Institute of Materia Medica of the Chinese Academy of Sciences suspected to have an influence on the "Amyloid formation, the inflammatory reactions in the brain and on the gut microbes".

Long ago, it is clear that it will not be a single substance or a single strategy, which could help in the future, people with Alzheimer's disease. And researchers and patients need a lot of patience. Add to that, that still is not understood what changes in the brain of Alzheimer's disease and which are simply normal aging processes. There, Andreas Monsch from the Memory Clinic wants to schedule. His Team is studying healthy aging processes (and seeking Volunteers from the age of 50 years, the agree to, studies to: www.memoryclinic.ch).

"in General, the success rates of newly approved drugs in the treatment of diseases of the Central nervous system is lower than in the treatment of cardiovascular or infectious diseases," says U.S. researchers Cummings. "But in the case of cancer research, it took 40 years, until new drugs come on the market. So far it is not in Alzheimer's research."

(editing Tamedia)

Created: 08.02.2019, 09:48 PM

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