Why drugs aren’t ultimately therapeutic

This 2016 Oregon review’s concept was the inadequacy of drug-based therapies, explored with the specific subject of epilepsy:

“Currently used antiepileptic drugs:

  • [aren’t] effective in over 30% of patients
  • [don’t] affect the comorbidities of epilepsy
  • [don’t] prevent the development and progression of epilepsy (epileptogenesis).

Prevention of epilepsy and its progression [requires] novel conceptual advances.”

The overall concept that current drug-based therapies poorly address evolutionary biological realities was illustrated by a pyramid, with the comment that:

“If the basis of the pyramid depicted in Figure 1 is overlooked, it becomes obvious that a traditional pharmacological top-down treatment approach has limitations.”

Why drug ultimately aren't therapeutic

I would have liked the reviewer to further address the “therapeutic reconstruction of the epigenome” point he made in the Abstract:

“New findings based on biochemical manipulation of the DNA methylome suggest that:

  1. Epigenetic mechanisms play a functional role in epileptogenesis; and
  2. Therapeutic reconstruction of the epigenome is an effective antiepileptogenic therapy.”

As it was, the reviewer lapsed into the prevalent belief that the causes of and cures for human diseases will always be found on the molecular level – for example, the base of the above pyramid – and never in human experiences. This preconception leads to discounting human elements – notably absent in the above pyramid – that generate epigenetic changes.

A consequence of ignoring experiential causes of diseases is that the potential of experiential therapies to effect “therapeutic reconstruction of the epigenome” isn’t investigated.

http://journal.frontiersin.org/article/10.3389/fnmol.2016.00026/full “The Biochemistry and Epigenetics of Epilepsy: Focus on Adenosine and Glycine”


Epigenetic remodeling creates immune system memory

This 2016 German review was of the memory characteristics of immune cells:

“Innate immune memory has likely evolved as an ancient mechanism to protect against pathogens. However, dysregulated processes of immunological imprinting mediated by trained innate immunity may also be detrimental under certain conditions.

Evidence is rapidly accumulating that innate immune cells can adopt a persistent pro-inflammatory phenotype after brief exposure to a variety of stimuli, a phenomenon that has been termed ‘trained innate immunity.’ The epigenome of myeloid (progenitor) cells is presumably modified for prolonged periods of time, which, in turn, could evoke a condition of continuous immune cell over-activation.”

The reviewers focused on the particular example of atherosclerosis, although other examples were discussed of epigenetic remodeling to acquire immune memory:

“In the last ten years, several novel non-traditional risk factors for atherosclerosis have been identified that are all associated with activation of the immune system. These include chronic inflammatory diseases such as:

as well as infections with bacteria or viruses.”

Innate immune memory

The reviewers also discussed diet, mainly of various diets’ negative effects.

I was interested to see a study referenced that used a common dietary supplement that’s also available in oatmeal:

“Pathway analysis of the promoters that were potentiated by β-glucan identified several innate immune and signaling pathways upregulated in trained cells that are responsible for the induction of trained immunity.”

Other research into the epigenetic remodeling of immune system memory includes:

http://www.sciencedirect.com/science/article/pii/S1044532316300185 “Long-term activation of the innate immune system in atherosclerosis”