Scientists uncover possible therapeutic targets for rare autism spectrum disorder

January 30, 2017

Researchers have uncovered 30 genes that could, one day, serve as therapeutic targets to reverse Rett syndrome, a rare neurological disorder that affects only girls and is a severe form of an autism spectrum disorder.

The study, led by scientists at Fred Hutchinson Cancer Research Center in Seattle, will be published January 30 in the Proceedings of the National Academy of Sciences.

There are currently no treatments specific to Rett syndrome, which affects approximately 15,000 girls and women in the U.S. and 350,000 around the world. Girls with Rett syndrome are born healthy and seem like any other baby up to one or two years of age. But then they start missing milestones and backslide in development.

"They have this period of normal development, and then it's taken away from them," said Dr. Antonio Bedalov, who led the study and is a clinical researcher at Fred Hutch. "It's devastating for the families."

The disorder is tied to a genetic defect in the MeCP2 gene, which is carried on the X chromosome. Girls, of course, have two copies of this chromosome but one X is silenced in every cell. Even though, on average, half of a girl's cells will produce the healthy version of this X-linked gene, the mutation in the other half of cells is enough to trigger the symptoms of the disorder.

Using adult mouse cells in the lab, Bedalov and his colleagues identified a way to partially reawaken the "inactive X," the X chromosome that is silenced in every cell. The researchers were also able to reactivate the normal copy of the MeCP2 gene.

Bedalov emphasized that the findings are still in the preclinical stage and that therapeutics are a long ways off.

But it's a start, Bedalov said. Because their approach leads to the reactivation of the entire chromosome, it could also apply to other, similar disorders that involve the X chromosome.
-end-
The Rett Syndrome Research Trust funded the project.

At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch's pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer with minimal side effects. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation's first and largest cancer prevention research program, as well as the clinical coordinating center of the Women's Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Private contributions are essential for enabling Fred Hutch scientists to explore novel research opportunities that lead to important medical breakthroughs. For more information visit fredhutch.org or follow Fred Hutch on Facebook, Twitter or YouTube.

Fred Hutchinson Cancer Research Center

Related Rett Syndrome Articles from Brightsurf:

Proteins -- and labs -- coming together to prevent Rett syndrome
Two labs investigated whether the disruption of one protein's condensate-forming ability contributes to Rett syndrome.

Genetic editing milestone in mouse model of Rett Syndrome
A genomic error that causes Rett Syndrome, a serious lifelong neurological disorder, can be corrected in the brains of mice by rewriting the genetic instructions carried by the RNA.

Yale researchers find potential treatment for Rett Syndrome
An experimental cancer drug can extend the life of mice with Rett Syndrome, a devastating genetic disorder that afflicts about one of every 10,000 to 15,000 girls within 6 to 18 months after birth, Yale researchers report June 10 in the journal Molecular Cell.

Research team investigates abnormal neuron activity in Rett syndrome
Research by Billy Lau, a postdoctoral researcher working with Assistant Professor Keerthi Krishnan at the University of Tennessee, Knoxville, examines the time during which an adult female mouse first learns to recognize and respond to the distress cries of young mouse pups as an opportunity for the brain to rewire and learn again.

A dietary supplement improves skills of an atypical Rett syndrome patient
Administration of the amino acid L-serine, a dietary supplement, contributes to the improvement of the communicative and motor skills of a patient with a mutation that alters glutamate receptors.

A new drug shows preclinical efficacy in Rett syndrome
A new article published in the Cell Reports describes how a new drug is able to reduce the symptoms and activate the dormant neurons characteristic of Rett Syndrome in preclinical models.

X chromosome reactivation could treat Rett syndrome, other X-linked disorders
A study from a team of Massachusetts General Hospital investigators points toward a potential strategy for treating X-linked disorders -- those caused by mutations in the X chromosome -- in females.

Discovery fuels hope for Rett syndrome treatment
Vanderbilt University researchers have relieved symptoms of Rett syndrome in a mouse model with a small molecule that works like the dimmer switch in an electrical circuit.

Drug improves brain performance in Rett syndrome mice
A brain penetrant drug -- a small-molecule mimetic of BDNF, or brain derived neurotrophic factor -- is able to improve brain performance in Rett syndrome mice -- specifically synaptic plasticity in the hippocampus and object location memory.

Small-molecule therapeutic boosts spatial memory and motor function in Rett syndrome mice
Rett syndrome is a neurological disorder affecting learning and development, caused by a mutation in the MECP2 gene triggering decreased levels of brain-derived neurotrophic factor (BDNF).

Read More: Rett Syndrome News and Rett Syndrome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.