Israeli study finds gene mutation that may cause some autism, possibly enabling treatment
About a million people worldwide have autism originating in mutation in SHANK3 gene
Reporter at The Times of Israel
In a breakthrough, Tel Aviv University researchers say they have identified a gene mutation in the brain that might be a cause of genetically based autism.
The discovery of the mutation in the SHANK3 gene, responsible for about one million cases of autism worldwide, could lead to effective treatment of that type of autism.
The study was led by Prof. Boaz Barak and doctoral student Inbar Fischer from the university’s School of Neuroscience and Psychological Sciences, Prof. Ben Maoz from the Faculty of Engineering, and Prof. Shani Stern from the University of Haifa’s Department of Neurobiology.
“This technology will help us develop treatments that could help ameliorate some of the symptoms of autism,” Barak and Fischer told The Times of Israel in a teleconference call.
The study was published two weeks ago in the peer-reviewed journal, Science Advances.
SHANK3 autism
People with SHANK3 autism, like other forms of autism, may have delayed or absent speech, difficulties with social interaction, motor impairment, and repetitive behaviors.
There is a spectrum of severity, however, and some people have milder symptoms or fewer intellectual impairments than others.
In a healthy brain, Barak said, cells send messages to one another via synapses. These synapses help people think, learn, talk, and feel.
But damage to the SHANK3 can disrupt these message transmissions, impairing the brain’s development and functioning. People with SHANK3 autism have faulty synapses that affect the communication network between the brain’s neurons.
“We know that the protein encoded by SHANK3 plays a central role in the brain’s proper communication,” Barak said.
Neurons receive information, he explained, “and receptors grab the information and transmit it to the next cell and then the next.”
The role of myelin
The researchers focused on brain cells known as oligodendrocytes, which produce myelin, a fatty layer that insulates nerve fibers.
“Myelin is critical,” Barak said. “Just like the covering on electrical cables in your house.”
The researchers hypothesized that SHANK3 plays an important role in creating the myelin, Fischer explained.
The scientists used a mouse model for autism with the same mutation that appears in humans with SHANK3 autism.
They observed that when the myelin is faulty, it does not insulate the neurons.
“This disrupts the transmission of messages between brain regions and impairs brain functioning,” Fischer said.
Finding a genetic fix
After understanding the problem, the researchers then sought a method for fixing the damage caused by the gene mutation.
The scientists took stem cells from the skin of a girl with SHANK3 autism identical to that of the mice. From these stem cells, they generated the gene sequence of a healthy SHANK3 gene sequence and introduced it to mutated cells.
“We succeeded in giving these cells the right sequence and improved the protein structure and function of the cells,” Fischer said. “This has the potential of [yielding] a genetic treatment to give to patients in the future.”
Fischer said that although the researchers did the work on mice cells, they added the human genetic sequence “to take it to the next level.”
“We know that this sequence works and may be developed in the future as a genetic therapy for autism treatment,” she said.
