Taking aim at autism…from many angles

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Finding a diagnostic tool and an effective treatment for autism are the end goals for Dr. Dorota Crawford, whether she is studying genetic markers for autism or examining how the environment in which a baby develops in utero may affect development of brain cells.About 190,000 Canadians suffer from Autism Spectrum Disorders (ASDs), which affect how the brain processes information and result in abnormal development and behaviours. One in 150 children is diagnosed with the disorders, usually by age three. ASDs lasts a lifetime, affecting a person’s ability to communicate, form relationships with others, and respond appropriately to the world. There is no simple test and no effective treatment.Crawford, an assistant professor in the School of Kinesiology & Health Science at York University, aims to change this. She is using her unique dual expertise in genetics and neuroscience research to study how genes that have been associated with autism affect brain cell development, and how environmental factors – for example, drugs or infections – may cause molecular changes that interfere with communication between neuronal cells in the developing brain.She is confident that breakthroughs in earlier diagnosis and treatment of the disorder will come from a multidisciplinary approach.Crawford’s lab at York University is one of very few autism labs in the world that integrates genetics with molecular and cellular neuroscience approaches to study the link between biological and environmental causes of autism and behaviours. She is a faculty member of the Neuroscience Graduate Diploma Program and also part of the interdisciplinary Autism Alliance Research Group in York’s Faculty of Health. By working together, researchers in the Autism Alliance are seeking to understand the whole individual, working from the level of genes to cells to behaviour and the family. Their research ranges from basic science to clinical outcomes: from studying how social signals such as facial expressions are processed by our brains, for example, to trying to improve the language and communication skills of children with autism. Crawford’s current study, in collaboration with Children’s Treatment Network in Richmond Hill, aims to isolate causative genes to improve understanding of what goes wrong in brain development.The study will identify genes that predispose infants to autism by analyzing simple, non-invasive cheek swabs volunteered by children and adults who have been diagnosed with the disorder. Using the cheek swabs, Crawford will be able to measure gene expression levels in people with autism (gene expression is the chemical process of translating genetic codes in DNA into a protein). Her hypothesis is that an excess or insufficient expression of a gene may contribute to brain deficits and the symptoms of autism because early brain development depends largely on gene expression. Crawford will analyze the genetic material derived from cheek swabs using powerful new microarray technology that is able to detect more abnormalities than standard genetic tests. The technique used in the study will be useful for diagnosis of autism earlier in life, says Crawford, and will enable the development of more individualized intervention programs and identification of potential therapeutic targets. Her laboratory at York has produced a number of important results already, using a state-of the art microscope imaging system funded by the Canada Foundation for Innovation and Ontario Research Fund, and research investment from the Natural Sciences and Engineering Research Council of Canada.A recently-published study by Crawford and York graduate student Javaneh Tamiji showed for the first time how the drug misoprostol, that was misused by pregnant women in Brazil to terminate pregnancies, actually interferes with neuronal cell function. The study shows that the drug reduces the number and length of neuronal extensions, which might prevent the cells from communicating with each other. The drug is not used by pregnant women in Canada. However, the study also describes that other factors – for example, infections or inflammations – might have similar effects and interfere with development of brain cells in utero.An earlier study in Crawford’s lab demonstrated how a gene mutation found in some people with autism appears to disrupt very early stages of brain development and contribute to the nervous system deficits that are the hallmarks of autism spectrum disorder.The study traced the link from a mutated gene found in individuals affected with autism to the molecular mechanisms of cell signaling that occur as the brain is developing. Crawford was able to take images of living neuronal cells from mice using the state-of-the-art microscope imaging system mentioned above. She provided evidence that the mutated gene can affect cells signaling molecules such as calcium and influence early brain development.“If we can identify affected genes and signaling pathways early in brain development – as we did in that study – then it should be possible to develop more effective treatments for children within three years of age,” says Crawford. For more information about Dr. Crawford’s developmental neuroscience laboratory, or to participate in autism studies, please visit http://www.yorku.ca/dakc/.