Declan Murphy at IMFAR 2014

This was the start of the International Meeting for Autism Research (IMFAR) and the opening speaker was a my good friend Declan Murphy from the Institute of Psychiatry at King’s College in London. I have known Declan ever since he came to train at the NIMH quite a few years ago. He has always distinguished himself for being a man of big ideas and a good sense of humor. The theme of his plenary presentation or keynote address was why are there so few effective treatments for autism and whether translational neuroscience can be of help in this regard?

Among the many reasons for a lack of successful treatments to autism, Declan was quick to point out that we have not been targeting core symptoms of the condition- at least not those that have been pinpointed by pathology. Other difficulties have included the many associated symptoms of the condition (e.g., anxiety, attention deficit), as well as difficulties in translating behavioral approaches into real life. Clinical trials are widely divergent in regard to the age range of the sampled population and, even within a trial, the age range may be a broad one considering the small number of patients. Declan believes that trial should better stratify the patient population and that this will be done in the near future with the aid of neuroimaging. Finally many participants (about one third of ASD individuals) may be receiving prescribed meditations which may offer confounds to outcome measurements.

Decaln Murphy

Dr. Murphy also tackled the large number of risk genes for ASD (over 1,000). Despite the vast numbers no single gene abnormality accounts for a significant number of patients (smaller than 1%). However, he emphasized that many of these risk genes were clustering around synaptogenesis. Dr. Murphy’s (and his collaborators) own research are now focusing on the excitatory/inhibitory imbalance of autism (see my previous blog on the origins of the excitatory/inhibitory theory of autism: https://corticalchauvinism.wordpress.com/wp-admin/post.php?post=2041&action=edit&message=10). He has extrapolated findings to humans from an animal model(Nlgn3 mouse model) that appears to have a deficiency of GABA and behavioral abnormalities reminiscent of autistic-like behaviors (Note: I do not abscribe to research that starts by developing an animal model and then calling it autistic, see https://corticalchauvinism.com/2013/01/20/of-mice-and-men-complications-of-animal-models-in-autism-research/). Dr. Murphy has now done studies (unpublished) with PET that show abnormalities of GABAa receptor in ASD in the nucleus accumbens, amygdala, and hippocampus. He is now onsidering ways of translating this finding into clinical trials.

In summary, his presentation emphasized the lack of knowledge in regards to the pathology of autism and therefore our inability to target pathological abnormalities in therapeutic attempts. Present attempts are not tailored to individuals (everybody receives the same things regardless of needs) and trials are underpowered given the small number of participants.

6 responses to “Declan Murphy at IMFAR 2014

  1. Anxiety is a huge problem for my 18 year old autistic son. He also has epilepsy. For well over a year now he has paced the house constantly, if under occupied, with his arms held high up to his chest, chest protruding forward, hands flopped down in front, head stretched back, eyes rolled back (at times). It has been very distressing to see this but we cannot divert or engage him when he is like this. I had the feeling that dystonia is coming in to play here but not too sure. Thank you for your post Manuel.

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  2. I would LOVE to enter my son into clinical trials — but as you noted, the drugs he takes often prohibit his participation. Or his dual Dx of cerebral palsy, or the fact that most studies want kids that have a certain IQ threshold or are verbal (this is AUTISM??). Also, if you don’t live near a big research center or major metropolitan area, there are no trials that would work for you. I live in Boulder, CO — hardly anything comes to the ATN facility at JFK Partners/Denver Children’s Hospital. If I hear of a study, I’m often too late to enroll him. Can’t there be a better way to promote study enrollment?

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  3. Dr. Casanova, Just saw this. Again, when I read this, I am convinced that this is the root cause for my daughter. Unfortunately she is currently hospitalized and going through the rounds in the medical system. Best regards, Prasanna

    Best regards, Prasanna

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