Abstract
Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research.
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Acknowledgements
I would like to thank T. Montine at Stanford University for his critical reading of the manuscript. This work was supported by the US Department of Veterans Affairs and the US National Institute on Aging (AG045034).
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T.W.-C. is scientific adviser to and founder of Alkahest Inc., a company developing blood-based treatments to increase health span.
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Wyss-Coray, T. Ageing, neurodegeneration and brain rejuvenation. Nature 539, 180–186 (2016). https://doi.org/10.1038/nature20411
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DOI: https://doi.org/10.1038/nature20411
Majid Ali
ECT and EBR Therapies for Drug-Resistant Major Depression
The words ?Making Connections? begin the text on the cover of Nature of 10 November, 2016. In the first article of Nature Insight in it, Wyss-Coray writes: ?Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain.?(ref. 1). Concerning brain rejuvenation, I offer some comments on the continuing use of the term electroconvulsive therapy (ECT) to treat major depression which is refractory to multiple drug regimens.
In 1961, as a third-year medical student at King Edward Medical College, Lahore, Pakistan, on my bicycle I took my 12-year-old sister, Majida Begum, for ECT treatments. During the procedure, the psychiatrist asked me to firmly hold the back of her head between my hands. On the return bicycle trips, she said nothing about ECT, nor did I.
ECT was first used in 1938. Ever since, the issues concerning consent for treatment have drawn much attention. A 2008 national Scottish audit found that that 23% of patients who received the treatment were incapable of giving informed consent (ref. 2) A 2005 British review found that only about half of patients felt they were given sufficient information about ECT and its adverse effects (ref. 3).
Many patients with major depression not responding to multiple drug regimens ask me for advice about ECT. Our conversation proceeds something like the following:
?My psychiatrist has recommended ECT treatment. I?m in terror of it. What do you think?? the patient asks.
?It is considered the most effective treatment for severe depression which does not respond to antidepressant drugs. I suggest an informed second opinion before you take ECT,? I reply.
?You do know what ECT is, don?t you?? the patient asks tersely.
?Yes, I do.?
?What does ECT stand for?? the patient asks rhetorically.
?ECT is short for electroconvulsive therapy,? I respond.
?Those words terrorize me,? he protests.
?Well, well ?,? I search for the right words.
?Well what? Is this what you want me to do? Convulse to get better? Is that your idea of healing?? he fires his questions with rising frustration.
I look at him in silence, wondering how I myself might react to the possibility of receiving ECT. In earlier years, I had not heard the expressions like ?re-booting the brain,? and ?clearing the cobwebs of the brain? for explaining how ECT works.
One day, I saw a patient who was palpably tormented by intense suffering of unrelenting depression. He engaged me in a similar conversation. I tried to plumb the depth of his suffering for some moments, then stammered, wishing to say the following:
We can call ECT energy therapy. That is what ECT really is. It is energy that filters and re-directs cellular cross-talk in the brain. Really, that is all what ECT is ? an energy therapy, just like electronic devices for pain control. It is energy that first puts you to sleep. You do not feel any pain. You wake up just as you do after sleep. Honestly, that is all what ECT is.
As words rolled from my lips, I saw the face of patient soften somewhat. We looked at each other in silence for long moments. Encouraged I continued. This healing energy works by silencing hurtful voices in the brain, switching off cycles of fear and panic, so to speak. Obliterating deep despair of falling through black bottomless abyss of depression.
The patient looks at me intently and then takes some deep breaths. I continue. Years ago, my younger sister received this form of energy therapy. She did not complain of pain, may be a little headache sometimes. Nothing more. Honestly, nothing more. I stop. Again, we look at each other, searching for the meanings of the words.
?Energy healing, eh!? he says with doubt.
?Yes, energy therapy.? I reply matter-of-factly.
?Energy healing to change cellular cross-talk in the brain, as you put it.?
?Yes. Yes. It is energy that rejuvenates the brain, in a manner of speaking.?
?It is really that simple, is it?? he asks, tensing up again.
?I can complicate it if you want,? I try to lighten up the conversation. ?We could call it brain re-birthing. Or may be just energy brain rejuvenation.?
Holistic View of Neurotransmission and Depression
In the same Nature Insight, Canter and colleagues write the following: ?Emerging functional data are also shifting the aetiological focus of the disease from a neuron-centric view to an integrated outlook that acknowledges the synergistic functions of the different cell types of the brain. Consistent with this holistic view, numerous disrupted processes are interconnected in AD and interact to provoke a cycle of dysfunction as the disease progresses.? (ref. 4)
The above words succinctly state my case for the science and philosophy of holism in understanding and treating depression (ref. 5), in addition to the case of Alzheimer?s disease, for which the above-cited paragraph was written. So began the thinking which led me to coin the term ?energetic brain rejuvenation therapy? - the ?EBR therapy,? for short. I add that in my mind, brain rejuvenation means functional restoration of oxygen signaling (ref. 6), insulin homeostasis (ref. 7), brain cell membrane redox equilibrium (ref. 8), and generation of neuronal membrane action potential that releases neurotransmitters from vesicles which store them. In my view, all of this cannot be achieved without integratively addressing relevant issues of nutrition, metabolism, gut microbiota, hepatic detoxification pathways, and the matters of fears, anger, and anxiety. (ref.5-8).
References
1.	Wyss-Coray. Ageing, neurodegeneration and brain rejuvenation. Nature 2016;539:180.
2.	Ferguson G, et al. (2009) The Scottish ECT Accreditation Network (SEAN) Report 2009. Retreived 2010.05.24.
3.	Rose D, Wykes T, Bindman J, et al. Information, Consent, and perceived Coercion: Patient?s perspective on Ectroconvulsive Therapy. British Journal of Psychiatry. 2005;186:54-59.
4.	Canter RG, Penney J, Tsai L-H. The road to restoring neural circuits for the treatment of Alzheimer's disease. Nature. 2016; 539, 187?196.
5.	Ali M. Depression ? An Overview. http://drali1.org/depressio....
6.	Ali M. Oxygen and Aging. (2nd ed.) New York, Canary 21 Press. 2004.
7.	Ali M. The Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.
8.	Ali M. Oxidative coagulopathy in environmental illness. Environmental Management and Health. 2000;11:175-191.
Har Katcher
When I first published the basic method of heterochronic plasma exchange (Katche HL "Studies that shed a new light on aging", Biochemistry (Moscow) 2013, and before Wyss-Cory signed for a patent), it was on a different basis from what Wyss-Coray and the Conboys, Amy Wagers are trying to accomplish – finding 'the' factor or factors that blood-borne aging depends on – when it is clear that concentration effects are important and a host of different molecules, only some of which are proteins maybe be signalling or effector molecules of aging processes. The most obvious examples are the exosome encapsulated miRNAs that have been found to be taken up by other cells, changing the behavior of the recipient cells, or the stable long, non-coding RNAs found in the blood (lncRNAs). I believe this is reductionism at its worst – taking apart the goose to discover the source of golden eggs. If young plasma is sufficient to revitalize many vital tissues (and young epithelial tissues are not hard to obtain- or produce) then it should be a matter of engineering to reproduce this technique and to maximize it, as unlike heterochronic parabiosis, plasma exchange is a medically approved technology more than seventy years old, that can replace virtually all of the blood plasma of an old person with young plasma. If significant rejuvenation of rats and mice can be obtained, when according to size differences an old rate would only get something like 1/3 of its plasma replaced by young plasma, imagine what the replacement of 90-something percent might bring? The caveat is that the plasma must be unchanged with regards to unknown parameters or at least as close as we can get to 'virgin' plasma.