MAR 12, 2017 12:02 PM PDT

Protein Linked to Fragile X and Autism is a Treatment Target

WRITTEN BY: Carmen Leitch

There is a lack of reliable treatment options for autism, due in part to a poor understanding of how the disease works on a molecular level. One known cause of autism is fragile X syndrome, which is understood to be caused by a problem with the FMR1 gene. While Fragile X is easy to diagnose, there is no therapy for the disorder. Investigators at Michigan State University (MSU) have made progress in the fight against this disease, discovering a protein that likely plays a critical role in the disorder. Their findings were reported in Nature Communications and are summarized in the following video, and they could eventually be a big benefit to people waiting for treatment.

Fragile X can be traced back to the silencing of the FMR1 gene, but in normal cells, the protein produced by that gene interacts with hundreds of targets, messenger RNA (mRNA) molecules, and it can help regulate the levels of those mRNAs. For this work, the researchers have manages to zero in on one critically important target. They have linked that target to many of the physiological and molecular manifestations of Fragile X.

“We began with 600-800 potential protein targets, searching for the equivalent of a needle in a haystack,” explained one author of the report, Hongbing Wang, MSU physiologist. “Our needle turned out to be ADCY1. When we compared levels of this protein in Fragile X mouse model to normal controls, we saw a 20-25 percent increase of ADCY1.”

To follow up on their findings, the researchers tested the impact of reducing levels of ADCY1; they found that autism-related behaviors were also reduced. Next, they observed that an increase in the level of ADCY1 protein resulted in an increase in neuronal signaling. When those levels were then reduced, the neuronal signaling also went down to a normal level. 

In neurons that are affected by Fragile X, they have an excess of features called dendritic spines. Those bumps are especially numerous in the Fragile X neurons but when the researchers reduced levels of the ADCY1 protein, the bumpy appearance of the affected neurons was improved.

This work could eventually be a benefit to patients. Finding a single culprit that’s likely causing so many of the symptoms makes the new data appealing to pharmaceutical companies, Wang said. “Our research has identified a key target and a new approach that could easily be pursued by pharmaceutical companies,” Wang continued. 

Already an experimental drug called NB001, which is a possible treatment for pain that passes the blood brain barrier, has shown some positive initial results. “We’ve shown an accessible target that, through treatment using NB001, suppresses activity. The next steps would be to test toxicity and optimization," said Wang.

Wang cautioned that these findings are still a long way from actually being used to treat patients. Future research should not only focus on drug targets; researchers could delve deeper into how these mechanisms are working in younger organisms since this work used an adult mouse model. It would also be important to know if an intervention could be used to help stem the developmental disorders that build throughout a child's life.

Learn more about Fragile X from the video from the CDC.

 

Sources: Michigan State University, National Human Genome Research Institute, Nature Communications

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
DEC 15, 2019
Technology
DEC 15, 2019
3D-Printed Pipette Technology Advances Laboratory Testing
The need to design a simple and inexpensive laboratory method for medical tests has encouraged new technology developed by the University of Connecticut re...
DEC 15, 2019
Clinical & Molecular DX
DEC 15, 2019
Apple Watch New Research App: A Boon to Women's Health
The Apple company, in 2018, enrolled more than 400,000 people in its Apple Heart Study conducted in partnership with Stanford University researchers....
DEC 15, 2019
Clinical & Molecular DX
DEC 15, 2019
Patients can Self-Inject Easily Using an Integrated Pre-Filled Syringe and Autoinjector
The patients suffering from chronic disease require a regular dose of medicines, either orally or as injections. To prevent a monthly visit...
DEC 15, 2019
Health & Medicine
DEC 15, 2019
3D-printed cell traps catch cancer cells on the move
The early stages of metastasis, or the spread of cancer cells from the primary tumor site, are incredibly difficult to detect by analyzing blood samples. F...
DEC 15, 2019
Immunology
DEC 15, 2019
The Immune System's Hand in Toxic Shock
While rare, toxic shock is a dangerous condition that acts fast and can be fatal. A new study identified a new target for treating toxic shock, a component...
DEC 15, 2019
Immunology
DEC 15, 2019
Predicting Death with Clinical Immune Indicators
Immune and inflammation status could help doctors predict which individuals are most at-risk for death. Results from a new study mark the first step toward...
Loading Comments...