AIMS Molecular Science, 2019, 6(3): 52-72. doi: 10.3934/molsci.2019.3.52 Research article Special Issues

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

1 LIMSI-CNRS, rue John Von Neumann, Université d'Orsay – Bât. 508, 91403 Orsay Cedex, France
2 CRIIGEN, 40 rue Monceau, Paris 8^ème, France

Received: , Accepted: , Published:

Special Issues: Molecular Mechanisms and Therapy of Autism Spectrum Disorders

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An interdisciplinary study of autism led to implicate the relatively poor degradation of synaptic serotonin, a molecule involved in brain development. Consequent metabolic imbalance ofmonoamine neurotransmitters is assumed to impede memory encoding across sleep stages, hence the building of aberrant neural structures linked with autistic symptoms. A medication can be derived from this theoretical approach, with the aim of regulating neuromodulation whereby proper neural networks may start growing over impaired ones. The Valproate anticonvulsant has been prescribed here for its contribution to the promotion of a relevant brain enzyme known as Monoamine oxidase A (MAOA). Whereas case-studies usually focus on a subset of symptoms for less than three months in mild to moderate autism, the evolution of every autistic symptom has been witnessed across one year in an 11-year boy with severe autism. Rapid improvement of sleep, followed by the rising of visual exploration, preceded positive shifts of the core symptoms noticeable nine months later, however still impeded by bursts of hyperactivity. The adjunctive medication of Methylphenidate psychostimulant permitted afterwards to increase the attention span without interfering with Valproate. Such combination of MAOA-inducer and psychostimulant eventually favored the gradual acquisition of social conditioning, without fully erasing poor habits issued from ten years of autism. Because restricted to a disease-modifying action, this dual therapy relies on accompanying educational assistance, as notably learnt from its exploratory monitoring. Other insights focus on specific biomarkers as well as functional polymorphisms of relevant genes promoters, with the aim of guiding future clinical trials.

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References

1. Kuo HY, Liu FC (2018) Molecular pathology and pharmacological treatment of autism spectrum disorder-like phenotypes using rodent models. Front Cell Neurosci 12: 422.

2. Uzunova1 G, Stefano PS, Hollander E (2016) Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics. World J Biol Psychiatry 17: 174–186.

3. Béroule DG (2018) Offline encoding impaired by epigenetic regulations of monoamines in the guided propagation model of autism. BMC Neurosci 19: 80.

4. Essa MM, Al-Sharbati MM, Al-Farsi YM, et al. (2011) Altered activities of monoamine oxidase A in Omani Autistic children-a brief report. Int J Biolog Med Res 2: 811–813.

5. Chauhan V, Gu F, Chauhan A (2016) Impaired activity of monoamine oxidase A in the brain of children with autism. Conference Abstract: 14^th Meeting of the Asian-Pacific Society for Neurochemistry.

6. Hensler JG, Artigas F, Bortolozzi A, et al. (2013) Catecholamine/serotonin interactions: Systems thinking for brain function and disease. Adv Pharmacol 68: 167–197.

7. Béroule DG, Encoding of memory across online/offline alternations, screencast of running computer simulation, 2016. Available from: https://perso.limsi.fr/domi/Movie-S1_DGB_nov16.mov.

8. Alwinesh MTJ, Joseph RBJ, Daniel A, et al. (2012) Psychometrics and utility of psycho educational profile-revised as a developmental quotient measure among children with the dual disability of intellectual disability and autism. J Intellect Disab 16: 193–203.

9. Baer DM, Wolf MM, Risley TR (1968) Some current dimensions of applied behavior analysis. J Appl Behav Anal 1: 91–97.

10. Wu JB, Shih JC (2011) Valproic acid induces monoamine oxidase A via Akt/Forkhead Box O1 activation. Mol Pharmacol 80: 714–723.

11. Whitton PS, Oreskovic D, Jernej B, et al. (1985) Effect of valproic acid on 5-hydroxytryptamine turnover in mouse brain. J Pharm Pharmacol 37: 199–200.

12. Treatment of Children With Autism Spectrum Disorders and Epileptiform EEG With Divalproex Sodium. Available from: https://clinicaltrials.gov/ct2/show/NCT02094651.

13. Lord C, Rutter M, Goode S, et al. (1989) Autism diagnostic observation schedule: A standardized observation of communicative and social behaviour. J Autism Dev Disord 19: 185–212.

14. Lord C, Rutter M, Le Couteur A (1994) Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 24: 659–685.

15. Renault D (2015) Compte-rendu de suivi Neuro-visuel du 24/07/2015, Unité Fonctionnelle Vision et Cognition, Fondation Ophtalmologique Adolphe de Rothschild (Hôpital Rothschild, Paris), 3 pages in French.

16. del Campo N, Chamberlain SR, Sahakian BJ, et al. (2011) The roles of dopamine and noradrenaline in the pathophysiology and treatment of attention-deficit/hyperactivity disorder. Biol Psychatry 69: 145–157.

17. Vanicek T, Spies M, Rami-Mark C, et al. (2014) The norepinephrine transporter in attention-deficit/hyperactivity disorder investigated with positron emission tomography. JAMA Psychiatry 71: 1340–1349.

18. Santos K, Palmini A, Radziuk AL, et al. (2013) The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and difficult-to-treat epilepsies. Dev Med Child Neurol 55: 654–660.

19. Gara L, Roberts W (2000) Adverse response to methylphenidate in combination with valproic acid. J Child Adol Psychop 10: 39–43.

20. Nicolini C, Fahnestock M (2018) The valproic acid-induced rodent model of autism. Exp Neurol 299: 217–227.

21. Christensen J, Grønborg TK, Sørensen MJ, et al. (2013) Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA 309: 1696–1703.

22. Chateauvieux S, Morceau F, Dicato M, et al. (2010) Molecular and therapeutic potential and toxicity of valproic acid. J Biomed Biotechnol 2010: 479364.

23. Gervain J, Vines BW, Chen LM, et al. (2013) Valproate reopens critical-period learning of absolute pitch. Front Syst Neurosci 7: 102.

24. Ajram LA, Horder J, Mendez MA, et al. (2017) Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder. Transl Psychiatry 7: e1137.

25. Ganai SA, Ramadoss M, Mahadevan V (2016) Histone Deacetylase (HDAC) Inhibitors-emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration. Curr Neuropharmacol 14: 55–71.

26. Fujiki R, Sato A, Fujitani M, et al. (2013) A proapoptotic effect of valproic acid on progenitors of embryonic stem cell-derived glutamatergic neurons. Cell Death Dis 4: e677.

27. Laeng P, Pitts RL, Lemire AL, et al. (2004) The mood stabilizer valproic acid stimulates GABA neurogenesis from rat forebrain stem cells. J Neurochem 91: 238–251.

28. Giorgio ED, Brancolini C (2016) Regulation of class IIa HDAC activities: It is not only matter of subcellular localization. Epigenomics 8: 251–269.

29. Al-Asmary S, Kadasah S, Arfin M, et al. (2014) Genetic association of catechol-O-methyltransferase val (158) met polymorphism in Saudi schizophrenia patients. Genet Mol Res 13: 3079–3088.

30. Le TV, Chu TTQ, Le BN, et al. (2019) Prevalence of autism spectrum disorders and their relation to selected socio-demographic factors among children aged 18–30 months in northern Vietnam, 2017. Int J Ment Health Syst 13: 29.

31. Lai DC, Tseng YC, Hou YM, et al. (2012) Gender and geographic differences in the prevalence of autism spectrum disorders in children: analysis of data from the national disability registry of Taiwan. Res Dev Disabil 33: 909–915.

32. Cohen IL, Liu X, Schutz C, et al. (2003) Association of autism severity with a monoamine oxidase: A functional polymorphism. Clin Genet 64: 190–197.

33. Hranilović D, Novak R, Babić M, et al. (2008) Hyperserotonemia in autism: The potential role of 5HT-related gene variants. Coll Antropol 32: 75–80.

34. Abeling NG, van Gennip AH, van Cruchten AG, et al. (1998) Monoamine oxidase A deficiency: Biogenic amine metabolites in random urine samples. J Neural Transm 52: 9–15.

35. Frye RE (2018) Social skills deficits in autism spectrum disorder: Potential biological origins and progress in developing therapeutic agents. CNS Drugs 32: 713–734.

36. Hellings JA, Weckbaugh M, Nickel EJ, et al. (2005) A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders. J Child Adol Psychop 15: 682–692.

37. Hollander E, Chaplin W, Soorya L, et al. (2010) Divalproex sodium vs placebo for the treatment of irritability in children and adolescents with autism spectrum disorders. Neuropsychopharmacology 35: 990–998.

38. Hirota T, Veenstra-Vanderweele J, Hollander E, et al. (2014) Antiepileptic medications in autism spectrum disorder: A systematic review and meta-analysis. J Autism Dev Disord 44: 948–957.

39. Takuma K, Hara Y, Kataoka S, et al. (2014) Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dentritic spine loss in a mouse model of autism. Parmacol Biochem Behav 126: 43–49.

40. Qin L, Ma K, Wang ZJ, et al. (2018) Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition. Nat Neurosci 21: 564–575.

41. McDougle CJ, Naylor ST, Goodman WK et al. (1993) Acute tryptophan depletion in autistic disorder: A controlled case study. Biol Psychatry 33: 547–550.

42. McDougle C, Naylor ST, Cohen DJ, et al. (1996) Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch Gen Psychiatry 53: 993–1000.

43. Boccuto L, Chen CF, Pittman AR, et al. (2013) Decreased tryptophan metabolism in patients with autism spectrum disorders. Mol Autism 4: 16.

44. Bird PD (2015) The treatment of autism with low-dose phenytoin: A case report. J Med Case Rep 9: 8.

45. Gupta V, Khan AA, Sasi BK, et al. (2015) Molecular Mechanism of monoamine oxidase A gene regulation under inflammation and ischemia-like conditions: Key roles of the transcriptions Factors GATA2, Sp1 and TBP. J Neurochem 134: 21–38.

46. Minkiewicz P, Darewicz M, Iwaniak A, et al. (2016) Internet databases of the properties, enzymatic reactions, and metabolism of small molecules-search options and applications in food science. Int J Mol Sci Dec 17: 2039.

47. Koenraad PM, Braber AF (2016) Use of nonanoic acid as an antimicrobial agent, in particular an antifungal agent, patent A61Q17/005 (Antimicrobial preparations), 1999. Available from: https://patents.google.com/patent/WO2001032020A2/en.

48. Meyer JH, Ginovart N, Boovariwala A, et al. (2006) Elevated monoamine oxidase A levels in the brain: An explanation for the monoamine imbalance of major depression. Arch Gen Psychiatry 63: 1209–1216.

49. Bacher I, Houle S, Xu X, et al. (2011) Monoamine oxidase A binding in the prefrontal and anterior cingulate cortices during acute withdrawal from heavy cigarette smoking. Arch Gen Psychiatry 68: 817–826.

50. Cathcart MC, Bhattacharjee A (2014) Monoamine oxidase A (MAO-A): A signature marker of alternatively activated monocytes/macrophages. Inflamm Cell Signal 1: e161.

51. Hviid A, Hansen JV, Frisch M, et al. (2019) Measles, mumps, rubella vaccination and autism: A nationwide cohort study. Ann Intern Med 170: 513–520.

52. von Ehrenstein OS, Ling C, Cui X, et al. (2019) Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. BMJ 364: l962.

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