What Might Autism Teach About Alzheimers Disease (AD)? What Might AD Teach About Autism?
Majid Ali, M.D.
140 West End Avenue, New York, NY 10023
What Might Bird Eggs Teach About Autism, Alzheimer’s Disease?
Bioenergetic and Molecular Roots of Autism – Mito-Myco-Minro Trio of PSP Autism Model
As narrated earlier in this report, three primary bioenergetics and molecular derangements were recognized as the primary roots of autism of core clinical significance in an investigative journey, of inquiry, hypothesis, clinical exploration, and laboratory studies extending over a period of eighteen years (1998-2016) were: (1) attenuated oxygen signaling, with respiratory-to-fermentative shift in mitochondrial ATP generation5-7: (2) mycotoxicosis, notably the production of fungal toxins known to impede mitochondrial enzymes; and (3) maladapted insulin homeostasis leading to insulin toxicity18-21
This trio of disruptions (in molecular biology of oxygen, insulin homeostasis, and gut microbiome) sets the stage for the development of the trio of symptom-complexes of autism involving speech, stability of mood, during the antenatal and postnatal phases of developmental neurobiology. This, succinctly stated, forms the core of (impeded) progenitor stem cell progression model of autism (the “PSP Autism Model”,)37-40 a unifying model that integrates all pathogenetic and clinical aspects of autism.
For ease of verbal and written communication, this trio was abbreviated as the “mito-myco-minro trio.” Specifically, this trio: (1) defines fundamental pathogenetic mechanisms underpinning PSP autism model37-40; (2) sharply focuses on elements that impede neuronal progenitor stem cell progression in the antenatal-postnatal continuum, which is essential for the development of speech, sociability, and stability of mood; (3) provides specific guidelines for designing therapeutic strategies and regimens for treating autism (presented in the third of this three-part report); and (4) provides sound scientific basis and/or rationale for future investigative work in developmental neurobiology.
It is noteworthy here that the underlying mechanism of action of all recognized maternal infectious, environmental, metabolic, and pregnancy-related risk factors of autism have in common among them the commonalities of the mito-myco-minto trio (see details in the section entitled Progenitor Cell Progression in the Antenatal and Postnatal Continuum). A body of data concerning the mito-myco-minto trio has been presented in past publications,1,9,,19,20 ,22 while newer data is presented in this three-part report.
, and Progenitor Stem Cell Progression
Birds keep faith in their eggs and are loyal to them. They nest knowingly, fully aware that they are guardians of their species. They keenly observe what emerges from their eggs and fully assure the conditions under which the eggs must be hatched and the chicks delivered. What might nesting and hatching teach about autism and Alzheimer’s disease? This question rising randomly was amusing first, then revealing. More could be learned about the essential commonality of these two diseases, one rooted in events before birth and the other in years prior to death, it seemed, than by any other question concerning the causes, clinical course, and possible therapeutics of the diseases.54 At a fundamental level, a progenitor stem cell may be visualized as an egg which can morph into a perfect rooster or simply rot, depending upon the conditions of hatching or rotting.
Progenitor stem cells are reserve eggs for repair and renewal in all cellular beings, in autism as well as Alzheimer’s disease. The pathogenetic and clinical context in the these two increasingly prevalent neurologic diseases seemingly are different. At bioenergetics and molecular levels, however, a deeper reflections brings out the essential sameness of the two. Specifically, In Alzheimer’s disease, the neuronal progenitor cells are rendered dysfunctional in their repair and renewal functions by toxicities of the mito-myco-minro trio as in autism (amply documented in this report.)
Neuronal progenitor stem cells are lineage-committed stem cells which have partially differentiated to structural and functional maturity of the specific neuronal cell type of their destiny.53-58 The developing brain is especially vulnerable to: (1) attenuated maternal oxygen signaling; (2) accentuated insulin signaling; and (3) disrupted states of gut ecology and microbiome. The PSP autism model was formulated with the following six tenets: (1) all aspects of the autism spectrum disorder (ASD) can be explained on the basis of impeded neuronal PSP during prenatal and postnatal life; (2) three primary factors that impede PSP are: (a) attenuated oxygen signaling; (b) accentuated insulin signaling, and (c) mycotoxicosis resulting from altered gut microbiota with dominance of fermenting over non-fermenting microbial species [“oxyphobes dominating oxyphiles”]; (3) oxygen signaling and insulin signaling are so intricately and inextricably intertwined that they need to be considered as two integral parts of one kaleidoscopic, fully integrated “oxygen-insulin signaling matrix”22; (4) all factors that impede PSP work in concert to amplify disturbances of developmental neurobiology; (5) clinical benefits of successful integrative treatment plans accrue from restoration of the oxygen-insulin signaling matrix and effective control of the mold allergy-to-altered gut-microbiome – to -oxyphobe dominance in gut microbiome – to mycotoxicosis continuum; and (6) clinical relapses occur with reappearance of previously operant PSP-impeding factors or the appearance of new PSP-impeding factors.
In the context of the evidence of the PSP autism model put forth and expounded in this report, no clear lines of demarcation between antenatal and postnatal progenitor cell progression or other dimensions of developmental neurobiology are deemed valid. Progenitor cell progression, then, is seen as a continuum of maternal and fetal energetic, molecular, metabolic, and differentiative dynamics.57-61 This is a crucial point from both pathogenetic and therapeutic perspectives, and calls for a sharp focus on the mito-myco-minro trio in all deliberations of diverse aspects of the case of an individual patient with autism.
The above are crucial considerations in the philosophy and science of holism in health and healing, and are discussed at length in Nature’s Preoccupation With Complementarity and Contrariety, Volume I41 as well as the 10th,11th, and 12th volumes28-30 of The Principles and Practice of Integrative Medicine Are devoted to them.