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SUMMARY:Understanding and treating autism: a dual approach based on the Ne
 uroarcheology concept   - Y Ben-Ari\, Neurochlore\, BABiomedical  and The 
 Ben-Ari Institute of Neuroarcheology  (IBEN- Marseille\, France)
DTSTART:20210712T143000Z
DTEND:20210712T153000Z
UID:TALK161347@talks.cam.ac.uk
CONTACT:Yonat Rum
DESCRIPTION:The developing brain is not a small adult brain: all ionic cur
 rents and patterns are unique to immature cells. Neurons follow developmen
 tal sequences with a progressive modification of their electrical properti
 es. Immature patterns help validating the formation of brain networks\, en
 abling cells to fire and connect together. I have suggested the neuroarche
 ology concept according to which that an insult -whether genetic or enviro
 nmental - deviates these sequences leading to neurons that remain “immat
 ure” in the adult brain\, with immature patterns and aberrant  connectio
 ns. These immature ensembles are the cause of the disorder 1! As Autism is
  “born” in utero\, it might be amenable to treatment relying on this c
 oncept. \nWe have adopted a dual approach\ni) an early prognosis of autism
  relying on maternity data (caly et al Sci.Rep. 2021). We developed a Mach
 ine Learning program that can analyze without any a priori large number of
  parameters – in France almost 120  per each maternity- and analyze them
  to provide a prognosis and to identify parameters that impact the decisio
 n (ASD or Neurotypic). Using this “Genesis ML” program\, we report tha
 t it is possible to identify almost 100% of babies that will not have an A
 SD diagnosis and a subpopulation of babies who will but with a precision o
 f 75%. Large trials in many French maternities\, European and possibly US 
 ones are now planned. If validated\, Genesis ML will provide a novel impor
 tant avenue to enable early identification of babies at risk of ASD. enabl
 e an early identification of babies at risk and use psycho-educative known
  to be more efficient when used early.\nii) We discovered 3 decades ago a 
 shift from neurons with High (Cl-)i levels and excitatory actions of GABA 
 to low levels and inhibitory GABA actions 2\,3. Now\, in autism\, many neu
 rons have high (Cl-)i levels as if they have remained immature. This is th
 e case in drug induced ASD\, Fragile X\, Rett syndrome and Maternal Immune
  Activation 4\,5\,6. Restoring low (Cl-)i levels & GABAergic inhibition wi
 th an antagonist of the main chloride importer -Bumetanide- attenuates aut
 ism severity.  \niii) Relying on these observations\, we have performed 2 
 phase 2 -including a pivotal phase 2B- trial showing that bumetanide atten
 uates the severity of autism7\,8. These results have been confirmed by 7 i
 ndependent pilot or double blind randomized trials. Eye tracking and brain
  imaging studies showed an amelioration of the communication and reduction
  of the activation of the amygdala. With the French pharmaceutic company S
 ervier\, we are now performing the final FDA/EMA approved phase 3  in Euro
 pe\, USA\, Brazil and Australia (400 children -2-18 years old)\, final res
 ults are expected september 2021 and if positive a treatment in the market
  early 2024. \nTherefore our approach from bench to bed has indeed shown t
 hat it might be possible to establish a prognosis at birth and using selec
 tive antagonists of immature neurons to attenuate the severity of autism. 
 Clearly to understand and treat autism\,  it is essential to determine the
  alterations occurring in utero that announce autism.      \nReferences:\n
  1.	Ben-Ari\, Y. Neuro-archaeology: pre-symptomatic architecture and signa
 ture of neurological disorders. Trends in Neurosciences (2008) doi:10.1016
 /j.tins.2008.09.002.\n2.	Cherubini\, E.\, Gaiarsa\, J. L. J. L. & Ben-Ari\
 , Y. GABA: an excitatory transmitter in early postnatal life. Trends Neuro
 sci. 14\, 515–519 (1991).\n3.	Ben-Ari\, Y. Excitatory actions of GABA du
 ring development: The nature of the nurture. Nat. Rev. Neurosci. 3\, 728
 –739 (2002).\n4.	Ben-Ari\, Y. The GABA excitatory/inhibitory development
 al sequence: A personal journey. Neuroscience 279\, 187–219 (2014).\n5.	
 Fernandez\, A. et al. The GABA Developmental Shift Is Abolished by Materna
 l Immune Activation Already at Birth. Cereb. Cortex 29\, (2019).\n6.	Tyzio
 \, R. et al. Oxytocin-mediated GABA inhibition during delivery attenuates 
 autism pathogenesis in rodent offspring. Science (80-. ). 343\, 675–679 
 (2014).\n7.	Lemonnier\, E. et al. Effects of bumetanide on neurobehavioral
  function in children and adolescents with autism spectrum disorders. Tran
 sl. Psychiatry (2017) doi:10.1038/tp.2017.10.\n8.	Lemonnier\, E. et al. A 
 randomised controlled trial of bumetanide in the treatment of autism in ch
 ildren. Translational Psychiatry (2012).\n\n
LOCATION:https://us02web.zoom.us/j/85130861934?pwd=c1l1czdNSFVaUzdtRDRPSlU
 3Q0VmZz09
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