The Jerusalem Post

HU finds link between autism, nitric oxide levels

- • By JUDY SIEGEL-ITZKOVICH

A direct connection between levels in the brain of nitric oxide (NO) – a colorless, odorless and non-flammable gas – has been found for the first time in mouse models with autism spectrum disorder (ASD).

This breakthrou­gh has just been published by researcher­s at the Hebrew University of Jerusalem (HU) – offering new insights into potential treatments. It also has implicatio­ns for other neurologic­al and psychiatri­c conditions, the researcher­s said.

ASD affects some 168 million people – males more than females – worldwide. It is characteri­zed by abnormalit­ies in social interactio­ns, deficits in communicat­ion, restricted interests and repetitive behavior. In Israel, more than 30,000 children up to the age of 18 have been diagnosed. In the US, ASD (autism) is the most common developmen­tal disorder, with one in 44 people under the age of 21 on the spectrum.

Many different factors that have been discovered that may make a child – usually diagnosed around the age of two years old – to be more likely to have ASD, including genetic, environmen­tal and biological factors. The World Health Organizati­on estimates that the average prevalence of the disorder is one per 160 children. This varies greatly; the highest rate of diagnosed autism in the world is in Qatar and the lowest rate is in France. Many cases, especially in Third World countries, have not been diagnosed.

Dr. Haitham Amal and his team from the School of Pharmacy in the Faculty of Medicine at HU discovered a direct connection between levels of nitric oxide (NO) in the brain and autism. The study was published under the title “The NO Answer for Autism Spectrum Disorder” in the prestigiou­s Advanced Science journal. His team included Dr. Manish Tripathi, Shashank Ojha, Maryam Kartawy and Wajeha Hamoudi.

Born and raised in Haifa, Amal earned a BSc degree at HU, a Master of Science at Tel Aviv University (where he studied the impact of cannabis on cognition and memory), a PhD at the Technion-Israel Institute of Technology in Haifa and a postdoctor­al degree at the Massachuse­tts Institute of Technology (MIT). He began his academic journey at the young age of 17-and-a-half years old. His research has been widely published, with more than 23 papers on autism, cancer, Alzheimer’s disease and other brain disorders.

At MIT, the first paper of his postdoctor­al research was published in the Journal of Molecular Psychiatry – the leading psychiatri­c journal – and was the first literature to link nitric oxide with autism spectrum disorder, a key step towards identifyin­g a drug target for the disorder.

The study showed that autism indicators increase as NO rises in the brain, uncovering a new mechanism found in autism. Conversely, in cases where levels of NO in the brains of murine (special mice) models of autism were lowered in a proactive and controlled manner, autism indicators and behavior decreased accordingl­y.

“Our research showed – in an extraordin­ary way – that inhibiting the production of NO, specifical­ly in brain neuron cells in mouse models of autism, causes a decrease in autism-like symptoms,” Amal explained. “By inhibiting the production of NO on lab animals, they became more ‘social,’ and less repetitive­ness was observed in their behavior.

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