Navigation Links
UNC child neurologist finds potential route to better treatments for Fragile X, autism
Date:10/23/2013

CHAPEL HILL, N.C. When you experience something, neurons in the brain send chemical signals called neurotransmitters across synapses to receptors on other neurons. How well that process unfolds determines how you comprehend the experience and what behaviors might follow. In people with Fragile X syndrome, a third of whom are eventually diagnosed with Autism Spectrum Disorder, that process is severely hindered, leading to intellectual impairments and abnormal behaviors.

In a study published in the online journal PLOS ONE, a team of UNC School of Medicine researchers led by neurologist C.J. Malanga, MD, PhD, describes a major reason why current medications only moderately alleviate Fragile X symptoms. Using mouse models, Malanga discovered that three specific drugs affect three different kinds of neurotransmitter receptors that all seem to play roles in Fragile X. As a result, current Fragile X drugs have limited benefit because most of them only affect one receptor.

"There likely won't be one magic bullet that really helps people with Fragile X," said Malanga, an associate professor in the Department of Neurology. "It's going to take therapies acting through different receptors to improve their behavioral symptoms and intellectual outcomes."

Nearly one million people in the United States have Fragile X Syndrome, which is the result of a single mutated gene called FMR1. In people without Fragile X, the gene produces a protein that helps maintain the proper strength of synaptic communication between neurons. In people with Fragile X, FMR1 doesn't produce the protein, the synaptic connection weakens, and there's a decrease in synaptic input, leading to mild to severe learning disabilities and behavioral issues, such as hyperactivity, anxiety, and sensitivity to sensory stimulation, especially touch and noise.

More than two decades ago, researchers discovered that in people with mental and behavior problems a receptor called mGluR5 could not properly regulate the effect of the neurotransmitter, glutamate. Since then, pharmaceutical companies have been trying to develop drugs that target glutamate receptors. "It's been a challenging goal," Malanga said. "No one so far has made it work very well, and kids with Fragile X have been illustrative of this."

But there are other receptors that regulate other neurotransmitters in similar ways to mGluR5. And there are drugs already available for human use that act on those receptors. So Malanga's team checked how those drugs might affect mice in which the Fragile X gene has been knocked out.

By electrically stimulating specific brain circuits, Malanga's team first learned how the mice perceived reward. The mice learned very quickly that if they press a lever, they get rewarded via a mild electrical stimulation. Then his team provided a drug molecule that acts on the same reward circuitry to see how the drugs affect the response patterns and other behaviors in the mice.

His team studied one drug that blocked dopamine receptors, another drug that blocked mGluR5 receptors, and another drug that blocked mAChR1, or M1, receptors. Three different types of neurotransmitters dopamine, glutamate, and acetylcholine act on those receptors. And there were big differences in how sensitive the mice were to each drug.

"Turns out, based on our study and a previous study we did with my UNC colleague Ben Philpot, that Fragile X mice and Angelman Syndrome mice are very different," Malanga said. "And how the same pharmaceuticals act in these mouse models of Autism Spectrum Disorder is very different."

Malanga's finding suggests that not all people with Fragile X share the same biological hurdles. The same is likely true, he said, for people with other autism-related disorders, such as Rett syndrome and Angelman syndrome.

"Fragile X kids likely have very different sensitivities to prescribed drugs than do other kids with different biological causes of autism," Malanga said.


'/>"/>

Contact: Mark Derewicz
mark.derewicz@unch.unc.edu
919-923-0959
University of North Carolina Health Care
Source:Eurekalert

Related medicine news :

1. Childrens National researcher co-authors study on transitioning cystic fibrosis care
2. Bradley Hasbro Childrens Research Center launches food allergy video game trial
3. Comfort & Harmony™ Congratulates Pregnant in Heels Star Rosie Pope on Pregnancy, Expecting Fourth Child
4. St. Jude Children’s Research Hospital Scientific Director Elected to Institute of Medicine
5. Focus on developmental approach to obesity in children and adolescents
6. For low-income families, substandard housing takes toll on children
7. St. Jude Childrens Research Hospital scientific director elected to Institute of Medicine
8. Children born to teen mothers have delayed development, likely due to social factors
9. Research shows genetic anti-inflammatory defect predisposes children to lymphoma
10. Moms weight gain during pregnancy tied to childhood obesity
11. Bcureful® Aids in the Development of New Tuberous Sclerosis Complex Center at Ann & Robert H. Lurie Children’s Hospital of Chicago
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/5/2016)... ... February 05, 2016 , ... The Muscular ... Louisiana Kitchen restaurants, launched the 14th annual “Appetite for a Cure” campaign on ... muscular dystrophy, ALS and related diseases that severely limit strength and mobility. ...
(Date:2/5/2016)... ... February 05, 2016 , ... ... George H. Van Allen have signed a joint enrollment and degree completion agreement. ... pathway toward associate and baccalaureate degrees at FHU|Dickson. , The agreement allows ...
(Date:2/5/2016)... ... February 05, 2016 , ... US Sports Camps ... in Dover, NH to direct high-performance kids yoga training. ChildLight Yoga Studio is centrally ... one hour from Boston. , ChildLight Yoga Studio founder Lisa Flynn expresses her excitement, ...
(Date:2/5/2016)... New York, New York (PRWEB) , ... February 05, 2016 , ... ... in gym use and find themselves having to wait longer to access the treadmills. ... on their New Year’s resolutions to lose weight and get in shape by joining ...
(Date:2/5/2016)... ... February 05, 2016 , ... Pivot Point ... Best in KLAS: Software & Services for HIT Implementation Support & Staffing report ... independently ranks vendor performance by healthcare executives, managers and clinicians representing over 4,500 ...
Breaking Medicine News(10 mins):
(Date:2/5/2016)... , February 5, 2016 ... new market research report "Fetal (Labor & Delivery) and ... Antepartum), Warmer, Incubator, Pulse Oximeter, Phototherapy/Jaundice Management Devices, CPAP, ... by MarketsandMarkets, This report studies the global market over ... is estimated at USD 6.28 Billion in 2015 and ...
(Date:2/4/2016)... 2016 For hospitals considering enrollment in the ... in the program, the Health Resources and Services Administration,s ... , Mega-Guidance , could have significant impact on plans ... September 2016. Essential Insights , Daniel ... summarizes the Mega-Guidance,s key proposed changes, including a new ...
(Date:2/4/2016)... FOSTER CITY, Calif. , Feb. 4, 2016 ... (the "Company") today announced it has entered into ... and Exchange Commission (SEC) fully resolving the SEC,s ... Practices Act (FCPA).  Under the terms of the ... total of $12.8 million, including disgorgement, pre-judgment interest ...
Breaking Medicine Technology: