There is not a single Autism-specific gene, just brain genes !

For decades, we have been repeatedly informed as an undisputable fact that Autism Spectrum Disorders (ASD) are “genetic”, with genetic mutations being responsible for 15 then 25% and probably all ASD. This more technical than conceptual approach has not led to a single treatment even at early stages, and no significant novel understanding of how the brain operates in utero when the disorder is triggered. There has always been a fascination for genetics and brain disorders, since it is easier to be understood by politicians and a wide audience public and as it enables to avoid blaming usual suspects including environmental causes, or stress-related and difficult living conditions during maternity. Yet, many studies have clearly illustrated the impact during pregnancy of pesticides, pollution, viral or microbial infections or stress. With the possible exception of families at risk in which these mutations are present, the genetic mutations are more likely part of a continuum of signals associating genes and environment.

The brief large audience paper published in Spectrum by David Ledbetter and Scott Myers stresses that “there is not a single gene specifically related to ASD, they are all brain genes mutations… They are associated with many other symptoms such as intellectual disability, ADHD, seizures, severe sensory problems and so on”. If these mutations are relevant to a whole spectrum of disorders, it stems that there are no “Autism networks” and studying one mutation (out of the several hundred suggested for ASD) will neither clarify the underlying mechanism nor provide a road to treatment. The fact that these mutations occur in utero and impact brain development clearly indicates that the correct avenue for treatments is to determine these alterations and identify possible targets for pharmaceutical treatments. The Neuroarcheology concept that I proposed over a decade ago (Ben-Ari 2008) posits that genes and “environment” operate in series and that in utero alterations generate networks of neurons that remain immature. The activity they generate are the final cause of the disorder. The good news are that agents capable of blocking selectively these immature neurons and networks are available, and indeed have been tested in clinical trials successfully with an ultimate final phase 3 being currently conducted (Lemonnier et al. 2017)(see http://autism-studies.com/).

Therefore, without adequate concepts the extraordinary technological discoveries fall short of providing innovative treatments. The fact that it is now quite easy and straightforward to identify mutations does not imply that this will lead to treatments. The brain reacts to insults or developmental deviations by various forms of reactive plasticity, and not taking this into account is incompatible with therapeutic strategies. To understand and treat ASD, all efforts must be focused on fetal and embryonic development combining animal and human observations.

Yehezkel Ben-Ari CEO Neurochlore

References :

  • Ledbetter D and Myers S. There are no autism-specific genes, just brain genes. Spectrum, the leading site for autism research news. March 23rd, 2021.
    https://www.spectrumnews.org/opinion/there-are-no-autism-specific-genes-just-brain-genes/
  • Ben-Ari, Y. Neuro-archaeology: pre-symptomatic architecture and signature of neurological disorders. Trends Neurosci. 31, (2008).
  • Lemonnier, E. et al. Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders. Transl. Psychiatry (2017).