Despite new findings and advances in Alzheimer’s research, the search for therapies that prevent the onset of incurable dementia or slow the progression has so far been unsuccessful.
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Several drug trials that were already in the clinical phase have been discontinued this and previous years. But the setbacks do not mean the end of the Alzheimer-Research. Because there are other promising therapy concepts. Some are already in the clinical test phase.
New research approaches should bring breakthrough
Until now, research had focused on using active substances against the so-called amyloid plaques (protein deposits) that form in the brain of Alzheimer’s patients. The unsuccessful studies had shown, however, that this therapy concept is in vain.
But there are other research approaches that Alzheimer’s experts are hoping for more. “There are currently over 30 substances against Alzheimer’s in clinical testing,” says Professor Agnes Flöel, neurologist at the Greifswald University Hospital. Many of them are already in the phase III test.
Beta-amyloid is split off from a larger precursor protein (amyloid precursor protein). Further peptide fragments attach to the peptide, so that deposits are formed which impair the function of the nerve cells and ultimately destroy them. (Source: Image material: GettyImages, adaptation: t-online)
Alzheimer’s research: The focus is on the tau protein
The German Society for Neurology points out in a press release that current research is now more focused on the tau protein, which is part of the so-called microtubules inside the cell. These smallest tubes are used for mass transport between the cells and their stability. In Alzheimer’s patients, the molecular structure of the tau protein has changed, so that tau fibers, so-called fibrils, are formed, which are deposited in the cells and lead to loss of function in cell communication and cell death. The substance leukomethylthioninium prevents the deposition of tau fibrils – the first promising study results are already available.
Other phase III studies are currently investigating so-called “small molecules”, which are supposed to protectively intervene in the metabolic processes of the brain cells by inhibiting certain enzymes or blocking receptors. In addition, so-called autophagy enhancers, which are intended to boost the body’s clearing of “cell waste”, are being investigated in phase IIb studies in patients in very early stages of Alzheimer’s disease.
Hope for vaccine against Alzheimer’s
Alzheimer’s vaccines have also been successfully developed and are now undergoing clinical testing. The vaccines cause the immune system to produce the body’s own Aβ antibodies, which “recognize” β-amyloid and the body can defend itself against it. “In the end, they have the same therapeutic target as the substances that have now been tested negatively, but the body’s own defense may be more effective,” says Flöel. Her conclusion is: “Alzheimer’s research is far from over and we are optimistic that some of the substances that are currently being tested will lead to significant therapeutic advances.”
The Alzheimer’s Association in the USA, which supports research into the disease, is also confident. “Although we know the obstacles, we have never been as optimistic as we are today,” says their manager James Hendrix. “We will not let up in our fight against this terrible disease.”
The failure of the aducanumab study
Two major clinical trials to test an Alzheimer’s drug had been canceled in March 2019 due to lack of prospect of success. They were already in phase 3 of the clinical trial. Analyzes by an independent panel of experts had shown that the antibody tested did not slow down the decline in mental performance as hoped. The pharmaceutical company Biogen had been testing the active ingredient aducanumab together with the Japanese pharmaceutical company Eisai since 2017 for the market launch.
Previous research had initially shown promising results. In 2016, Biogen researchers, together with Swiss scientists, reported in the journal “Nature” that antibody therapy reduces protein deposits that can be found in the brain of Alzheimer’s patients. In addition, the deterioration in mental performance seemed to be slowing. The researchers had examined patients at a very early stage of the disease.
Further failures in Alzheimer’s research
Previously, the pharmaceutical companies Pfizer and LaRoche had also stopped their Alzheimer’s research because promising Alzheimer’s medication had failed in patient tests. This included the active ingredient crenezumab, which was considered a beacon of hope. The research results are negative and the drug did not achieve the intended study goal, Roche said. However, the pharmaceutical company plans to continue researching and developing other Alzheimer’s drugs.
Roche is one of a long list of failures in the development of therapies for Alzheimer’s that have not been coming for years. Since 2016, experimental funds from Eli Lilly, AstraZeneca, Johnson & Johnson and Merck have failed. Over 100 clinical studies have so far not shown any effective therapy for the previously incurable dementia. The drugs that are currently on the market can only alleviate the symptoms.
David Reynolds, chief scientist at the British non-profit organization Alzheimer’s Research UK, confirms that efforts to treat Alzheimer’s with drugs are making little progress and that research projects have been stagnating for a long time. “The companies have put a lot of time, effort, and money into it over the past 25 years, but there have been no new drugs on the market in 16 years.”
Alzheimer’s research: Few drugs tested
According to the website “Alzforum”, which collects data on possible new Alzheimer’s drugs, fewer than 300 preparations have at least reached test phase II. And only five drugs have been approved for the treatment of Alzheimer’s symptoms such as memory loss. To date, there is no medicine available to prevent the disease from progressing or even curing it.
Reynolds emphasizes that there are far fewer medications tested in the field than other widespread serious diseases. Around a hundred Alzheimer’s drugs are currently in the test phase, but more than a thousand drugs against cancer. One reason is that “pharmaceutical companies are ultimately companies”: “They are committed to their investors.” The expensive Alzheimer’s research, in which so far no breakthrough has been achieved, is simply not attractive for many pharmaceutical companies.
Dementia: The number of people affected is increasing
There would be enough potential customers. According to the German Alzheimer Society, around 1.6 million people in Germany alone are considered to have dementia today. About two thirds of them have Alzheimer’s. The World Health Organization (WHO) states that around ten million people worldwide are diagnosed with dementia every year, and two thirds of these are Alzheimer’s cases.
By 2030, the number of people affected worldwide is expected to increase to 82 million, and by 2050 to 152 million. This is also due to the fact that older people in particular suffer from Alzheimer’s and life expectancy is increasing worldwide. The consequences for the relatives, who often take on the extensive care of Alzheimer’s patients, and for the economies are enormous.
Pharmaceutical companies rely on other research projects
Nonetheless, in the past decades, pharmaceutical companies have primarily invested money in researching cardiovascular diseases and cancer, which particularly often lead to death. “When dementia there was no such investment, “Reynolds sums up. Therefore, little is known about the disease. To this day, the scientists are not exactly sure how Alzheimer’s develops.
It’s a nightmare for drug developers. Pfizer announced in early 2018 that it would conduct research on Alzheimer’sdrugs adjusting. Two days later, the Danish company Lundbeck announced that its idalopirdin development did not stop the cognitive decline in Alzheimer’s patients. Shortly thereafter, the biotech company Axovante announced that it was no longer working on its Intepirdin agent.
German Society for Neurology (NDN)
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