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The failure of several drug trials against Alzheimer's disease last year mitigated, but not destroyed, the hope of a cure
For Patients desperately waiting for a cure for Alzheimer's disease, the flow of bad news must appear relentless. During the past year, Janssen, Pfizer, Merck, AstraZeneca, Eli Lilly and Lundbeck are some of the pharmaceutical companies that have stopped Alzheimer's trials while their formerly promising drug candidates, N & D. Have not achieved satisfactory results. While there is still a lot of research going on, some of the most promising avenues now seem to have reached a dead end and there is a real risk that research funding will begin to slow down.
Inhibitors of the secretase cleavage enzyme (BACE). These are intended to prevent or reverse the accumulation of beta-amyloid, which agglomerates to form plaques in the brain that, in turn, appear to be linked to Alzheimer's disease. Some early results of tests of BACE inhibitors were very promising. Lanabecestat, a recently retired candidate from Eli Lilly and AstraZeneca, has gone as far as the Phase III trials with an accelerated designation from the US FDA. However, hopes that the enzyme beat would prevent the plaques and cure the disease have proved too optimistic.
For starters, the link between enzymes and Alzheimer's disease is more complex than it seemed: post-mortem studies reveal older people die with plaques and tangles in their brains without showing signs of dementia. On the other hand, even when the plates are reduced, relief to the brain appears to be only mild and temporary. In addition, in some cases, BACE inhibitors have disturbing side effects. Janssen's drug candidate, atabecestat, for example, was linked to high rates of harmful liver enzymes
New Avenues
According to Professor Clifford Jack of the Mayo Clinic, one possibility is that BACE inhibitors Attack the disease too late: the plaques began to cause irreversible damage to the brain long before the onset of dementia. He argues that Alzheimer's disease is the culmination of decades of molecular changes, nerve damage and brain degeneration, and that it is essential to look earlier in the chain of events. So, hope is based on one of two options. The first is that researchers can find early biomarkers of the disease and then develop new ways to prevent it from developing in the first place.
Professor Jack and his team are now examining five biomarkers that could prove significant in cerebral degeneration. They are not alone. The European Consortium for the Prevention of Alzheimer's Disease, for example, is working with 38 research organizations and recently enrolled its 800th participant in what is supposed to be a global biomarker study. Finding appropriate biomarkers is now considered the preferred means of healing, but if it turns out to be successful, it can pose ethical problems: people with Alzheimer's disease may very well need of immediate treatment, even in good health.
A second option has also emerged, aimed at targeting subsequent biological processes in the Alzheimer's process, those related to tau and cellular dysfunction. Such treatments could include stem cell injections that would seek to regenerate the brain or, more likely, drugs to support neuronal functions so that they can continue to function despite plaques and tangles. But, according to Professor Jack's hypothesis, such treatments would probably only slow the progression to dementia or manage the symptoms. Nevertheless, this seems to be where pharmaceutical companies are concentrating their research and development (R & D) efforts while waiting to see how early biomarkers develop.
Investment in R & D
still in the game, that's it. Given the small gains achieved so far through their investments in Alzheimer's R & D, it's not surprising that many companies are re-evaluating their strategy. In the case of Pfizer, in June, she announced that she would abandon R & D in Alzheimer's and Parkinson's disease, removing approximately 300 jobs at her facilities in the US states of Mbadachusetts and Connecticut . Not later than in October 2017, the US drug manufacturer, in partnership with Germany's Boehringer Ingelheim, had four experimental drugs against Alzheimer's disease, as well as one for the disease Parkinson's. But now he will instead launch a new venture capital fund focused on neuroscience research projects.
Others proved to be more robust. Eli Lilly was forced to cut 485 jobs following the failure of some of his Alzheimer's trials, including a major trial on Solanezumab, his main candidate. Nevertheless, having invested £ 125 million in Alzheimer research over the past 25 years, he is determined to continue his research, either by returning to the basics of research, or by testing his existing candidates on different groups of people. tests with different profiles. Similarly, Merck, despite the end of a trial for its verubecestat candidate in February, is preparing to complete another on the same drug, targeting those who are at an early stage of the disease.
Their determination is admirable and can ultimately be profitable. . After all, according to Alzheimer's Disease International, the number of people with dementia in the world is nearly doubling every 20 years, suggesting that it will reach 75 million by 2030 and 131.5 millions by 2050. Alzheimer's disease is the most common type of dementia. 62 percent of people diagnosed. And given the amount of care these people need, even those who manage to avoid this debilitating disease will be extremely grateful for any cure.
Ana Nicholls is Director of Industrial Operations at the Economist Intelligence Unit
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