Autism-modifying therapy based on the promotion of a brain enzyme: An introductory case-report

Béroule, Dominique

doi:10.3934/molsci.2019.3.52

Cited by 2 publications

(7 citation statements)

References 45 publications

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“…The relatively poor degradation of 5-HT assumed here would only initiate visible effects in the early childhood, when the third metabolizer (MAOB) is mature enough to supply the baseline catabolism of DA. This enzymatic reading provides an explanation for the regressive feature of ASD, while the X-inactivation and COMT polymorphism (low to high expressions) can together account for the male prevalence (Béroule, 2018(Béroule, , 2019. Consequent structural deficits are represented by a GP network in which the local 5ht parameters decrease slower than Ne across offline encoding, inducing either aberrant or lacking memory pathways (Béroule, 2016).…”

Section: Shared Brain Enzymatic Pathwaysmentioning

confidence: 99%

“…Temporary improvements have been reported in autistic individuals who experienced fever (Yim et al, 2017 ; Grzadzinski et al, 2018 ) or followed an antiepileptic treatment based on VPA (Hollander et al, 2001 ; Aliyev and Aliyev, 2018 ; Béroule, 2019 ). As introduced above, such reduction of symptoms is surprising because both medical conditions can also produce adverse effects during pregnancy (Patterson, 2011 ; Meador et al, 2013 ).…”

Section: Two Molecules In Questionmentioning

confidence: 99%

“…Gradual improvements arose across a broad autism spectrum, some of them showing up only 9 months after the trial beginning, and sometimes disturbed by bursts of overactivity. In order to remedy the latter, methylphenidate could complete VPA at the pharmacological level, without mutual interference (Béroule, 2019 ). This favorable outcome has been corroborated by a double-blind placebo-controlled trial of the same VPA-based drug, involving 100 children and using a global rating scale of ASD; 80% of the treated subjects showed significant global improvement, compared with 12% in subjects having received a placebo (Aliyev and Aliyev, 2018 ).…”

Section: Two Molecules In Questionmentioning

confidence: 99%

“…Through daily intake, VPA primarily protects against epilepsy. A preliminary trial led to its association with the methylphenidate psychostimulant for balancing the monoaminergic metabolism (Béroule, 2019 ). By comparison, the possible natural production of propionate and butyrate by the microbiome, following a process for initiating the relevant change (Kang et al, 2017 ), may be preserved by a high-fiber diet.…”

Section: The Microbiome Resourcesmentioning

confidence: 99%

“…From a clinical point of view, this global prediction can be tested on the occasion of future trials concerning MAOA-inducing molecules. Relevant biomarkers have been proposed (Béroule, 2019 ), including the periodic control of sleep electroencephalogram (EEG), levels of monoamines, their metabolizers and metabolites, and, if possible, the family phenotyping of selected genes responsible for the management of monoamines.…”

Section: Conclusion: Natural Fatty Acids Under Focusmentioning

confidence: 99%

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Paradoxical Effects of a Cytokine and an Anticonvulsant Strengthen the Epigenetic/Enzymatic Avenue for Autism Research

Béroule¹

2020

Front. Cell. Neurosci.

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Maternal exposure to the valproate short-chain fatty acid (SCFA) during pregnancy is known to possibly induce autism spectrum disorders (ASDs) in the offspring. By contrast, case studies have evidenced positive outcomes of this anticonvulsant drug in children with severe autism. Interestingly, the same paradoxical pattern applies to the IL-17a inflammatory cytokine involved in the immune system regulation. Such joint apparent contradictions can be overcome by pointing out that, among their respective signaling pathways, valproate and IL-17a share an enhancement of the “ type A monoamine oxidase ” (MAOA) enzyme carried by the X chromosome. In the Guided Propagation (GP) model of autism, such enzymatic rise triggers a prenatal epigenetic downregulation, which, without possible X-inactivation , and when coinciding with genetic expression variants of other brain enzymes, results in the delayed onset of autistic symptoms. The underlying imbalance of synaptic monoamines, serotonin in the first place, would reflect a mismatch between the environment to which the brain metabolism was prepared during gestation and the postnatal actual surroundings. Following a prenatal exposure to molecules that significantly elicit the MAOA gene expression, a daily treatment with the same metabolic impact would tend to recreate the fetal environment and contribute to rebalance monoamines, thus allowing proper neural circuits to gradually develop, provided behavioral re-education. Given the multifaceted other players than MAOA that are involved in the regulation of serotonin levels, potential compensatory effects are surveyed, which may underlie the autism heterogeneity. This explanatory framework opens up prospects regarding autism prevention and treatment, strikingly in line with current advances along the gut microbiome–brain axis.

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Section: Shared Brain Enzymatic Pathwaysmentioning

confidence: 99%