Not from cancer, but from Alzheimer's
A second chance for a cure
Alexandra Bruter, <url>
A new cure for Alzheimer's disease was proposed by scientists from Yale University (Kaufman et al., Fyn inhibition rescues established memory and synapse loss in Alzheimer's mice).
It is noteworthy in this medicine that it is not so new – the substance AZD0530 was developed as a cancer drug by the pharmaceutical giant AstraZeneca. But as a cure for cancer, it has not shown any encouraging results, and would have been forgotten if not for a new NIH project. The National Institutes of Health (NIH) is the main government body in the United States regulating biomedical research. A significant part of government funding is distributed by them.
They recently launched a project giving non-working medicines a second chance. In order for clinical trials of a new drug to begin in humans, it must be effective in treating animal models of the disease. Then you need to get permission from the regulatory authorities, and you can start testing on humans. The first stages of clinical trials are more devoted to proving the safety of the drug, investigating possible side effects and dose selection. Quite a few people participate in them, often no more than a dozen volunteers, but all this takes not so little time. By the third phase of clinical trials, the number of participants in some cases can reach several thousand, but usually the numbers are much more modest. Based on the results of the third phase, a decision is usually already made on the admission of the drug to the market, but the study continues after that.
Sometimes the understanding that the drug is ineffective comes after the release to the market, and very often – just during the third phase. By this point, a lot of time and money has been spent on the development and research of the drug (pharmaceutical companies usually put these costs into the prices of successful effective drugs).
But the human body is very complicated, and this gives medicines that have proved ineffective against any one disease a second chance. For example, the protein with which the drug should interact may be involved in the regulation of several processes at once. Or a not very effective inhibitor of one protein due to its spatial structure will be an effective inhibitor of another. A similar story came out with the most popular drug sildenafil (known as "Viagra"): it was developed for the treatment of coronary heart disease, but the blood flow in the coronary vessels did not improve, but it improved in the pelvis (for more information about this and other similar cases, see the note "Side effects or new properties?").
This is not a very rare situation, but such an effect is not so easy to detect. In fact, it is impossible to accidentally see that a drug is effective against another disease if the test participants do not suffer from this second disease. That is, it is necessary that the effect can be observed in healthy people (as in the case of sildenafil), or that people suffering from the second disease also turn out to be among the test participants.
But still, in some cases, based on our knowledge about the structure of wildlife in general and the human body in particular, we can assume exactly where the medicine may be effective.
The substance AZD0530 (saracatinib) – inhibits the kinases of the Sfk family. Kinases are regulatory proteins that activate other proteins by phosphorylating them. As a rule, increased kinase activity is associated with faster cell growth and reproduction. Therefore, out-of-control kinases are often found in tumor cells. In some cases, their out-of-control turns out to be the direct cause of the malignant transformation of the cell, sometimes it simply makes the tumor that has already appeared more aggressive.
In general, kinases are involved in many cellular processes, and it is not their activity itself that leads to pathology, but excessive activity. Excessive kinase activity (excessive phosphorylation of tau protein) is one of the aspects of the pathogenesis of Alzheimer's disease.
It is widely known that the symptoms of Alzheimer's disease are caused by the aggregation of an improperly folded protein, beta-amyloid. It is less well known that in addition, abnormal tau protein is present in the brain cells of patients. There is no consensus among scientists about which mechanism contributes more to pathogenesis. Normally, phosphorylated tau protein stabilizes microtubules - components of the cytoskeleton. But with excessive phosphorylation of tau protein (excessive activity of the corresponding kinases), it can no longer support the cytoskeleton, but instead sticks together into lumps. And the stability of the cytoskeleton for neutrons is especially important because of their specific shape.
Therefore, the authors of the work suggested that if AZD0530 is used as a tau protein kinase inhibitor, then the symptoms of Alzheimer's disease will recede. Mice with Alzheimer's disease were given medications for four weeks and found that their spatial memory improved (they began to navigate the maze faster). Improvements were also noticeable at the cellular level. It is noteworthy that there were no changes in the metabolism of beta-amyloid, that is, the results of the work rather indicate that the anomaly of tau protein, rather than beta-amyloid, makes a decisive contribution to the symptoms.
Portal "Eternal youth" http://vechnayamolodost.ru03.04.2015