Insulin and Alzheimer's disease
Johnson and Johnson recently announced the termination of clinical trials of a drug against Alzheimer's disease due to safety concerns. This failure has joined the list of a dozen large and expensive clinical trials that have shown no effect in the treatment of this disease.
Such a number of failures should make us think – do we really know the causes of Alzheimer's disease?
In the first description of the disease, the German doctor Alois Alzheimer (Alois Alzheimer) noted unusual changes in the brain of the deceased patient. He identified two types of protein aggregates that were not found in the brains of younger people: some accumulated between brain cells, others inside cells. These proteins were later identified as beta-amyloid and tau protein.
Alzheimer himself recommended that scientists avoid a one-sided approach to determining the causes of the disease. Unfortunately, his warning was ignored, and over the years the claim that the accumulation of these proteins causes Alzheimer's disease has become an axiom.
One of the problems was that it was impossible to test the correctness of this theory in an experiment. Only recently have we developed a technology that allowed us to determine the role of these proteins. And this is clearly not what scientists expected. For example, genetically modified mice with human beta-amyloid accumulating in their brains show only moderate disorders.
But the pharmaceutical industry decided that amyloid was the main culprit, and it has since become a target for anti-Alzheimer's drugs. They reduce the level of beta-amyloid in the brain either by suppressing synthesis or by removing it from brain tissue. Both approaches have been tested by different methods, different types of drugs have been created. None of these studies have shown any significant effects. Some major pharmaceutical companies, including Pfizer, have abandoned research in this area altogether.
Negative research results prove that amyloid protein is not the cause of Alzheimer's disease. Some companies have switched to tau protein. But pharmaceutical companies continue to use a one-sided approach, believing that a single protein is the cause of the disease.
Perhaps it's time to rethink the understanding of Alzheimer's disease. One of the new approaches is the search for genes that increase the risk of developing the disease. Its disadvantage is that there are few such genes, and they are rare. Apparently, Alzheimer's disease is caused by gene mutations.
Another option is to assess the risk factors for Alzheimer's disease. One of them is type 2 diabetes. Insulin in diabetes mellitus does not cope with the regulation of blood glucose levels. But it also performs other functions, for example, it is a growth factor.
Neurons are highly dependent on growth factors, and die when they are deficient. Probably, the cells become vulnerable to stress, the ability of the brain to repair damage that accumulates over time decreases.
When studying brain samples of patients suffering from Alzheimer's disease, researchers found that insulin ceases to function as a growth factor, even if the person did not suffer from diabetes. This observation suggests that diabetes medications may be an effective remedy against Alzheimer's disease. Animal studies show impressive results, clinical studies are underway.
Testing of antidiabetic drugs on animal models of another neurodegenerative disorder, Parkinson's disease, also showed impressive results.
Two clinical studies in patients with Parkinson's disease have proven their protective effect. In one of them, patients suffering from type 2 diabetes mellitus did not have Parkinson's-related impairments for two years, unlike the control group who received standard treatment. Another study was larger and with placebo control, it confirmed this result: there was no deterioration in the antidiabetic therapy group during 12 months of follow-up.
These results support the new theory that Alzheimer's and Parkinson's diseases are caused, at least in part, by a lack of growth factor activity in the brain.
The new theory gives a fresh look at how these diseases develop, and increases the likelihood of developing new effective treatment regimens.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of The Conversation: Alzheimer's disease: why insulin is a new suspect.