Tremble, Alzheimer's
Alzheimer's disease seems to suffer one defeat after another
Polina Loseva, "The Attic"
No drug against Alzheimer's disease has yet worked in controlled experiments. Nevertheless, scientists and doctors do not give up their attempts. Someone is trying to boost the patients' own immunity, someone suggests slowing down the aging of the body as a whole. And the Cortexyme company came from the other end: they assumed that microbes were to blame for everything, and developed their own antibacterial drug, which showed an encouraging result in the first trials.
Alzheimer's disease is a neurodegenerative disease that affects more and more people, still incurable. Probably, the reason for this "epidemic" is that the world population is aging, and the main risk factor for Alzheimer's disease is age: from 55 to 85 years, the risk of dying from it increases 700 times. American scientists fear that Alzheimer's disease will not only cause a serious blow to the population, but sooner or later will ruin the country's insurance budget. However, despite many studies devoted to the search for a cure, it has not yet been found.
Today, the new issue of Science Translational Medicine published an article Rapamycin and Alzheimer's disease: Time for a clinical trial?, the authors of which tried to explain the reason for this failure. They called their colleagues working in this field and concluded that people simply do not dare to conduct clinical trials. Someone is not sure of success and is afraid of not justifying the money spent (and only the National Institute of Aging in the USA spends half of the annual budget on finding a way to cope with Alzheimer's disease), someone is not ready to repeat therapy in humans that works on mice, because mice do not fully reproduce the symptoms of the disease.
The authors of the article themselves – American gerontologists Matt Caberlen and Veronica Galvan – propose to approach the problem radically. Since the main risk factor is age, that is, in fact, the aging of the body, it is possible to fight aging as a whole, simultaneously slowing down the development of the disease. As a therapeutic agent, they offer rapamycin, a medicine with a stormy history and many medical applications. It is known that rapamycin partially blocks the metabolism in cells, preventing them from spending too much energy and wearing out intracellular molecules. The authors hope that the argument in favor of the use of rapamycin in this area will be the data of recent clinical studies, according to which it is safe and even stimulates the immune defense of the body.
Simultaneously with the article on rapamycin, another, already experimental work was published in the latest issue of Science Advances (Dominy et al., Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors). An international group of scientists supported by a private pharmaceutical company Cortexyme has found a link between Alzheimer's disease and bacterial infection. The authors consider the bacterium to be the culprit of the disease Porphyromonas gingivalis, which often causes periodontitis (inflammation of the connective tissue at the base of the tooth), but can occur in the microflora and in healthy people. This bacterium has long been associated with the risk of developing Alzheimer's disease and cognitive impairment.
The authors of the study suggested that the bacterium affects the brain through its gingipain proteins. This is a group of enzymes that protect the microbe from an immune attack, partially digest nutrients in the environment, and also destroy tissue, helping bacteria to get inside it. In 96% of patients with Alzheimer's disease, gingipaines were detected in the brain, on the surface of neurons.
Gingipains (red) in the brains of patients with Alzheimer's disease. Neurons are colored yellow, astrocytes (auxiliary cells of nervous tissue) are green. Photo by Cortexyme, Inc.
In the course of further work, scientists have confirmed that bacterial infection itself can cause Alzheimer's disease: in mice infected with the microbe, beta-amyloid appeared in the brain – an accumulation of proteins characteristic of this disease and leading to damage to the nervous tissue. At the same time, amyloid proved to be a protection against gingipaines: it damaged not only its own neurons, but also bacterial cells. Thus, Alzheimer's disease can probably play the role of a protective mechanism in this case. The situation was saved with the help of a substance codenamed COR388, which blocks gingipaines. Under the influence of COR388, less beta-amyloid was formed in the brain of mice, and the number of bacteria decreased. That is, in fact, COR388 works as a narrow-spectrum antibiotic.
This study was submitted for publication at the end of May 2018. While the journal was evaluating the article and preparing it for publication, Cortexyme managed to launch and complete the first phase of clinical trials of COR388. At this stage, the safety of the drug for healthy people and patients with Alzheimer's disease was evaluated; the drug did not cause significant side effects. Moreover, the authors noted positive dynamics in patients, but in order to be sure of the effectiveness of the drug, the following phases of trials will be needed. The company plans to hold them in 2019.
At the same time, another company, United Neuroscience, claims success. Their way of fighting the disease is fundamentally different: this is a vaccine, that is, a drug assembled from beta-amyloid particles. Immune cells develop an immune response against it and in the process destroy beta-amyloid in the brain. The vaccine has already passed several stages of clinical trials and seems to show positive results. However, a small sample does not yet allow us to draw unambiguous conclusions about the effectiveness of the method.
Portal "Eternal youth" http://vechnayamolodost.ru