Featured Research

from universities, journals, and other organizations

Scientists design molecule that reverses some fragile X syndrome defects

Date:
September 4, 2012
Source:
Scripps Research Institute
Summary:
Scientists have designed a compound that shows promise as a potential therapy for one of the diseases closely linked to fragile X syndrome, a genetic condition that causes mental retardation, infertility, and memory impairment, and is the only known single-gene cause of autism.

Scientists on the Florida campus of The Scripps Research Institute have designed a compound that shows promise as a potential therapy for one of the diseases closely linked to fragile X syndrome, a genetic condition that causes mental retardation, infertility, and memory impairment, and is the only known single-gene cause of autism.

Related Articles


The study, published online ahead of print in the journal ACS Chemical Biology September 4, 2012, focuses on tremor ataxia syndrome, which usually affects men over the age of 50 and results in Parkinson's like-symptoms -- trembling, balance problems, muscle rigidity, as well as some neurological difficulties, including short-term memory loss and severe mood swings.

With fragile X syndrome, tremor ataxia syndrome, and related diseases, the root of the problem is a structural motif known as an "expanded triplet repeat" -- in which a series of three nucleotides are repeated more times than normal in the genetic code of affected individuals. This defect, located in the fragile X mental retardation 1 (FMR1) gene, causes serious problems with the processing of RNA.

"While there is an abundance of potential RNA drug targets in disease, no one has any idea how to identify or design small molecules to target these RNAs," said Mathew Disney, a Scripps Research associate professor who led the study. "We have designed a compound capable of targeting the right RNA and reversing the defects that cause fragile X-associated tremor ataxia."

Preventing Havoc

In tremor ataxia syndrome, the expanded triplet repeat leads to the expression of aberrant proteins that wreak widespread havoc. The repeats actually force the normal proteins that regulate RNA splicing -- necessary for production of the right kind of proteins -- into hiding.

The compound designed by Disney and his colleagues not only improves the RNA splicing process, but also minimizes the ability of repeats to wreak havoc on a cell.

"It stops the repeat-associated defects in cell culture," Disney said, "and at fairly high concentrations, it completely reverses the defects. More importantly, the compound is non-toxic to the cells. It looks like a very good candidate for development, but we're still in the early stages of testing."

Overall, this study reinforces Disney's earlier findings showing it is possible to identify and develop small molecules that target these traditionally recalcitrant RNA defects. In March of this year, Disney published a study in the Journal of the American Chemical Society that described a small molecule that inhibited defects in myotonic dystrophy type 1 RNA in both cellular and animal models of disease.

"We've gotten very good at targeting RNA with small molecules, something a lot of people said couldn't be done," Disney pointed out. "Our approach is evolving into a general method that can be used to target any disease that is associated with an RNA, including, perhaps, fragile X syndrome itself."

The new compound also works as a probe to better understand how these repeats cause fragile X syndrome and how they contribute to tremor ataxia, Disney added.

In addition to Disney, authors of the study, "Small Molecule That Targets r(CGG) and Improves Defects in 2 Fragile X‑Associated Tremor Ataxia Syndrome," include Biao Liu, Wang-Yong Yang, Tuan Tran, and Jessica L. Childs-Disney of Scripps Research; and Nicolas Charlet-Berguerand and Chantal Sellier of the Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM), the Centre National de la Recherche Scientifique (CNRS), and University of Strasbourg, Illkirch, France.

The study was funded by the National Institutes of Health (award numbers 3R01GM079235-02S1 and 1R01GM079235-01A2), INSERM, the French National Research Agency, and The Scripps Research Institute.


Story Source:

The above story is based on materials provided by Scripps Research Institute. Note: Materials may be edited for content and length.


Journal References:

  1. Matthew D. Disney, Biao Liu, Wang-Yong Yang, Chantal Sellier, Tuan Tran, Nicolas Charlet-Berguerand, Jessica L. Childs-Disney. A Small Molecule That Targets r(CGG)expand Improves Defects in Fragile X-Associated Tremor Ataxia Syndrome. ACS Chemical Biology, 2012; 120904130429000 DOI: 10.1021/cb300135h
  2. Raman Parkesh, Jessica L. Childs-Disney, Masayuki Nakamori, Amit Kumar, Eric Wang, Thomas Wang, Jason Hoskins, Tuan Tran, David Housman, Charles A. Thornton, Matthew D. Disney. Design of a Bioactive Small Molecule That Targets the Myotonic Dystrophy Type 1 RNA via an RNA Motif–Ligand Database and Chemical Similarity Searching. Journal of the American Chemical Society, 2012; 134 (10): 4731 DOI: 10.1021/ja210088v

Cite This Page:

Scripps Research Institute. "Scientists design molecule that reverses some fragile X syndrome defects." ScienceDaily. ScienceDaily, 4 September 2012. <www.sciencedaily.com/releases/2012/09/120904170924.htm>.
Scripps Research Institute. (2012, September 4). Scientists design molecule that reverses some fragile X syndrome defects. ScienceDaily. Retrieved October 26, 2014 from www.sciencedaily.com/releases/2012/09/120904170924.htm
Scripps Research Institute. "Scientists design molecule that reverses some fragile X syndrome defects." ScienceDaily. www.sciencedaily.com/releases/2012/09/120904170924.htm (accessed October 26, 2014).

Share This



More Health & Medicine News

Sunday, October 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
Toxin-Packed Stem Cells Used To Kill Cancer

Toxin-Packed Stem Cells Used To Kill Cancer

Newsy (Oct. 25, 2014) — A Harvard University Research Team created genetically engineered stem cells that are able to kill cancer cells, while leaving other cells unharmed. Video provided by Newsy
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins