Today I'll point out an example of drug reuse and autophagy upregulation. The processes of autophagy are responsible for recycling molecular waste and broken cellular structures. Autophagy is upregulated in response to stress placed upon cells, whether by heat, cold, lack of nutrients, a toxic local environment, and so forth. This is beneficial to tissue function, health, and longevity, and thus there is considerable interest in the research community in producing therapies that boost the operation of autophagy.
This hasn't made a great deal of progress towards the clinic, but nonetheless in any of the sizable databases of small molecule compounds there are some that result in increased autophagy – the question is always whether the side-effects are tolerable.
The cancer research community in particular tests a great many compounds and attempts to influence a great many core cellular processes, autophagy included. So when we see attempts at drug reuse, it is often the case that the drug in question is a small molecule that is either present used, used in the past, or was at least considered for chemotherapy. In the trial noted here, the drug is nilotinib.
Researchers propose that it produces the observed reduction of toxic protein aggregates in the Alzheimer's disease brain by spurring increased autophagy, and can do so at low enough doses to avoid the worst of the side-effects noted to date. Of course, as is sadly standard in the mainstream of Alzheimer's development, no benefit to patients was observed to accompany improvements in biomarkers. The commentary provided by the trial administrators regarding the need more patients to see possible improvements is what is normally said by trial administrators about treatments that are expected to have only small and unreliable beneficial effects.
This is all par for the course. An entirely too sizable fraction of modern medical development centers not around the development of new therapies, based on new advances in science, but rather finding existing therapies that can be reused in new ways. This, I think, is one of the important underlying reasons as why most new treatments tend to be only marginally effective.
The present regulatory structure makes it so costly and difficult to explore new approaches that funding entities are steered into the path of using whatever is already to hand, provided it can be shown to do at least a little good. The edifice of medical development is built of perverse incentives such as this, unfortunately.
Source: Fight Aging!