Study finds unexpected new target to treat autism symptoms

Researchers at The Ottawa Hospital and the University of Ottawa were able to reverse certain behavioural symptoms in a mouse model of autism by fixing a problem in the brain blood vessels. Their findings, published in Neuron, present a promising new treatment target for these symptoms.

Autism is a neurodevelopmental condition with widely varying characteristics. Some of the behavioural symptoms can make life more challenging. While many people with autism have found ways to manage these symptoms, no drug treatment exists. 

“The road from discovery to clinical trials is long, but we’re excited by the possibility that our findings might one day improve the daily lives of people with autism,” said senior author Dr. Baptiste Lacoste, senior scientist at The Ottawa Hospital and professor at the University of Ottawa. 

Dr. Lacoste’s team previously discovered that blood vessels in the brain don't work properly in mouse models with a 16p11.2 deletion, one of the most common genetic mutations seen in autism. They were the first to look at what was happening in the blood vessels of the brain. 

The researchers found the problem began in cells lining the blood vessels, called the endothelial cells. These cells make sure blood quickly gets to the parts of the brain that are active. This responsive blood supply is needed for proper brain function. 

However, the endothelial cells in these mice don’t respond quickly enough. This happens early in brain development and causes behavioral symptoms later in life, including hyperactivity, repetitive movements, and motor learning impairment.

In this new study, driven by former PhD student Dr. Julie Ouellette, the research team looked at what was wrong with these endothelial cells and whether it could be fixed. 

The team led by Dr. Lacoste found that the endothelial cells had half the normal level of a molecule called ATP. ATP is usually considered an energy molecule, but in this case the cell was missing its target, called a P2Y2 receptor, on its surface. 

By activating this P2Y2 receptor, the researchers could restore the cell’s function, increase blood flow in the brain and reverse the behavioral symptoms in adult mice. This was achieved using a drug known to activate P2Y2 and currently approved for humans in Japan and South Korea to treat dry eye syndrome. 

“It’s as if these cells are asleep, and now we can wake them up,” says Dr. Lacoste. “And we may only need to treat them once to wake them up permanently. We will test that further, but it’s an encouraging feature for a future treatment.” 

This study only looked at adult mice. This means targeting P2Y2 could reverse behavioural symptoms that were already well established.  Next, the team plans to treat mice earlier in life to see if early treatment has additional benefits. 

The team has also filed a patent application for using P2Y2 activation in the blood vessels to treat autism symptoms. They are interested in exploring drug development with the aim of eventual clinical trials.

Full reference: Purinergic receptor activation rectifies autism-associated endothelial dysfunction. Julie Ouellette, Sareen Warsi, Phinea Romero, Purva Khare, Shama Naz, Leya Aubert-Tandon, Moises Freitas-Andrade, Chantal Pileggi, Sozerko Yandiev, Joanna Raman-Nair, James Yee, Nicole Blakeley, Balaji Govindaswamy, Cesar Henrique Comin, Mary-Ellen Harper, Devika Soundara Manickam, Fabrice Dabertrand, Armen Saghatelyan, and Baptiste Lacoste. Neuron. DOI: 10.1016/j.neuron.2026.09.009. September 30, 2026

Core resources: University of Ottawa Metabolomics Core Facility, Cell Biology and Image Acquisition Core Facility and Electron Microscopy Core Facility.

The Ottawa Hospital (TOH) is one of Canada’s top learning and research hospitals where we are guided by our vision to provide the world-class and compassionate care we would all want for our loved ones. Our multi-campus hospital, affiliated with the University of Ottawa, is home to the Regional Trauma Centre and Cancer Centre, and to discoveries that are adopted globally. Backed by generous support from the community, we are focused on reshaping the future of health care to improve the health of our diverse population of patients from Eastern Ontario, Western Quebec, and Nunavut. All researchers at The Ottawa Hospital follow a Responsible Innovation Framework for developing and commercializing innovations in a responsible way. For more information on research at The Ottawa Hospital, visit ohri.ca. 

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