Researchers at Tel Aviv University have identified a genetic mutation in the brain that may be responsible for genetically-based autism.
The discovery of the SHANK3 gene mutation, which accounts for approximately one million cases of autism worldwide, could lead to effective treatments for this type of autism.
The study was conducted by Professor Boaz Barak and doctoral student Inbar Fischer from the School of Neuroscience and Psychological Sciences, Professor Ben Maoz from the Faculty of Engineering, and Professor Shani Stern from the Department of Neurobiology at the University of Haifa.
"This technology will help us develop treatments that may improve some symptoms of autism," Barak and Fischer stated during a teleconference with the Times of Israel.
The study was published two weeks ago in the peer-reviewed journal Science Advances.
Individuals with SHANK3 autism, like other forms of autism, may experience language delays or may not speak at all, social interaction difficulties, motor impairments, and repetitive behaviors. However, there is a spectrum of severity, with some individuals exhibiting milder symptoms or fewer intellectual disabilities than others.
In a healthy brain, Barak explained, cells communicate through synapses, which enable thinking, learning, speaking, and feeling. However, lesions in the SHANK3 gene can disrupt these message transmissions, hindering brain development and function. Individuals with SHANK3 autism have defective synapses that affect communication networks between brain neurons.
"We know that the protein coded by SHANK3 plays a central role in proper brain communication," Barak noted.
Neurons receive information, which receptors capture and transmit to the next cell, and so forth.
The researchers focused on brain cells known as oligodendrocytes, which produce myelin, a fatty layer that insulates nerve fibers. "Myelin is essential," Barak explained. "It is like the insulation on electrical cables in your home." The researchers hypothesized that SHANK3 plays an important role in myelin creation, Fischer explained.
They used a model of autistic mice with the same mutation as found in humans with SHANK3 autism. They observed that when myelin is defective, it fails to insulate neurons. "This disrupts message transmission between brain regions and alters brain function," Fischer stated.
After understanding the problem, the researchers sought a method to repair the damage caused by the genetic mutation. Scientists collected stem cells from the skin of a girl with SHANK3 autism identical to that of the mice. From these stem cells, they generated the genetic sequence of a healthy SHANK3 gene and introduced it into the mutated cells.
"We succeeded in giving these cells the correct sequence and improving the structure and function of the proteins in the cells," Fischer stated. "This could lead to a genetic treatment to be administered to patients in the future." Although the researchers worked on mouse cells, they added the human genetic sequence "to take it to the next level."
"We know this sequence works and could be developed in the future as a genetic therapy for treating autism," she concluded.