Experimental drugs rewire brain connections in autism

page with definition of autism
A new study has revealed that a gene linked with autism plays a different role than the one that had been accepted so far.
New research from the University of Texas Southwestern in Dallas has identified two potential new treatments for autism spectrum disorder, targeting the impact of a faulty gene on neural communication.

Autism — which is often used as an umbrella term for autism spectrum disorder (ASD) — is characterized by repetitive behaviors, impaired social communication, and very focused interests.

According to estimates from the Centers for Disease Control and Prevention (CDC), around 1 in 68 children in the United States has been diagnosed with ASD.

Treatments for ASD are often focused on addressing the behavioral symptoms and helping people with the disorder to learn better communication strategies. So far, relatively few efforts have targeted the biological causes of autism.

Now, researchers from the University of Texas Southwestern in Dallas are exploring the route of learning more about these biological factors in order to address them directly.

The study, led by Dr. Craig Powell, has identified two potential treatments that could restore the neurotransmission processes affected by the absence of a gene known as KCTD13.

Dr. Powell and team published the results of their research in the journal Nature.

Missing gene ‘impairs brain function’

The KCTD13 gene encodes a protein with the same name, and previous studies have linked its expression level with abnormal brain size, arguing that “[b]oth the loss and the gain of [the chromosomal segment that contains this gene] confer a significant risk of autism and developmental delay.”

Dr. Powell and colleagues’ research, however, revealed that KCTD13 plays an entirely different role: it is not tied not to brain size but to synaptic transmission, or neurotransmission. This is the neurons’ ability to transmit information.

The researchers also identified drugs that may be able to reverse the faulty connectivity that comes as a result of this gene’s deletion.

The deletion of this gene impairs brain function in a major way, and we found a way to repair the damage. But we have more work to do before we try these treatments on people. The findings give us a clue as to what pathways are altered and where to look.”

Dr. Craig Powell

Dr. Powell and team used mice to investigate what the KCTD13 protein actually does, as well as what role it plays in autism.

In their experiments, they deleted the gene that encoded the protein in mice, and noted that its absence halved the number of synaptic connections in the animals’ brains.

The researchers noticed that in the absence of KCTD13, the levels of a protein known as RhoA increase, which impairs synaptic transmission.

In its normal expression, KTCD13 helps to regulate this protein, allowing neurons to communicate freely.

Scientists test drugs with high potential

To counteract the effect of the gene deletion, Dr. Powell and team administered different types of RhoA-inhibiting drugs to the mice: Rhosin and Exoenzyme C3.

This approach was successful, restoring the animals’ normal synaptic transmission in under 4 hours.

The researchers note that Exoenzyme C3 is currently being tested in clinical trials for the treatment of spinal cord injury. If successful, they hope that these trials will smoothen the path for further tests of the drug’s potential in ASD treatments, as well.

In the meantime, Dr. Powell urges scientists to focus their efforts on additional studies of the KCTD13 gene, whose complex role in the context of neurotransmission is yet to be fully understood.

He notes the importance of investigating the role of other genes contained in the chromosomal segment that includes KCTD13.

“This is an important step, but there is a long road ahead,” says Dr. Powell. “Now we need to better understand the function of other genes in this chromosomal region and how these may lead to brain dysfunction and the behavioral changes we call autism.”

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