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Posts tagged ‘Autism Genome Project’

Guest Post: The Twinkle Light Model of Autism and the Brain

By Nathalia Holt

Little wisps of blonde hair peek through before Eleanor’s head pops up from behind the chair. She gives me a big smile, a wave, and then runs off, yelling ‘bye-bye’ at the top of her little lungs. Eleanor is our first child, she’s twenty-months-old, constantly oscillating between feisty and willful, silly and sweet. At this age it’s almost as if you can see the neurons connecting in her brain, each new experience bringing the world closer to her tiny baby fingers. As a scientist and nervous first time mom, I know that twenty months is not only a critical age in development but also the best time to catch the early symptoms of autism spectrum disorder.

A decade ago, diagnosing a child younger than three with autism was unheard of. In the years since, several studies have shown us that when autism is caught sooner, before two years old, and is accompanied by early therapy, the outcome is better. Children receiving early therapy not only have significantly higher IQs, but their everyday skills, like brushing teeth and having dinner with their family, are improved. These findings have led to a push in early intervention. After a study published in the Journal of Pediatrics last year, many pediatricians use an autism questionnaire at the twelve-month check-up. The idea being, the sooner the disease is spotted, the sooner it can be treated, and the better the ultimate outcome.

This year the CDC reported a shocking increased prevalence in autism. The number of children being diagnosed is up 78% since 2002. This statistic has sparked fiery debate. Once centered on the debunked role of vaccines, today we have new questions to argue about. Is increased prevalence the result of increased awareness? Better screening? An unknown environmental contributor? Does a genetic basis exist?

There are a few things we do know about the cause of autism. Autism tends to run in families. Supported by the Autism Genome Project, hundreds of patients have had their genomes screened. The findings have been remarkable; certain mutated genes are highly associated with the disease, seemingly passed down across generations. These genes encode synaptic proteins, proteins that bridge neurons and are critical to the collective electrical signaling of the nervous system. Think of these networks like a strand of twinkle lights. When the wires connecting the bulbs together begin to fray, the entire strand stops working properly, blinking in and out. Intriguingly, these genes are implicated in other neurodegenerative diseases such as Alzheimer’s and Parkinson’s. However, this research has been seriously hampered by the lack of an animal model for autism. After all, what kinds of experiments are safe to do in children?

Researchers at several universities have addressed this by knocking out the function of these genes in mice. They then painstakingly followed their behavior, tracking their social interaction and communication. They found that mice with the mutated version of these genes displayed hyperactivity, repetitive grooming and abnormal vocal and social behavior, in essence, the classic symptoms of autism. For the first time, a clear physiological mechanism for autism has been uncovered.

Building on this, research published in Nature this past June, shows that there may be a way to improve the social behavior of these genetically impaired mice. By stimulating the proteins lost in autism-associated genes, researchers were able to rescue the function of a signaling molecule on the surface of neurons that is critical to memory and learning. This treatment lifted the telltale signs of autism, resulting in mice with normal social interaction.

This month, new research, pursuing innovative, early therapies for autism was published in Nature. Researchers treated a mouse model of Dravet’s syndrome, characterized by impaired learning and autism spectrum behavior, with a drug called clonazepam. Treatment with this drug completely rescued the social behavior of the mice by repairing communication between genetically impaired neurons. This exciting work is the latest chapter in a new trend in studies that highlight the genetic foundation behind some autism disorders as well as the potential for new childhood therapies.

Autism is complex; this type of treatment may or may not result in a viable future therapy. Yet this work has the potential to usher in a new wave of autism therapy, one in which we are able to map genetics to brain function, where children receive personalized therapy specific to their genetic make-up. We’re not there yet, but as I fret over my toddler’s building social skills, I’m hopeful about the future of autism.

Nathalia Holt, Ph.D. is an HIV fellow at the Ragon Institute of MGH, MIT and Harvard University. Nathalia is interested in how the individual experiences of patients and physicians influence medical research. She is currently writing on her first book, THE TWO BERLIN PATIENTS, exploring the personal stories behind two of the most influential HIV cases and the future of the epidemic, to be published by Dutton/Penguin. Nathalia lives in Boston, MA with her husband and baby daughter. Follow her blog and on twitter @nathaliaholt.