Navigation Links
Scientists uncover image of muscular dystrophy defect & design targeted drug candidates
Date:1/2/2014

JUPITER, FL, January 2, 2013 Scientists from the Florida campus of The Scripps Research Institute have revealed an atomic-level view of a genetic defect that causes a form of muscular dystrophy, myotonic dystrophy type 2, and have used this information to design drug candidates with potential to counter those defectsand reverse the disease.

"This the first time the structure of the RNA defect that causes this disease has been determined," said TSRI Associate Professor Matthew Disney, who led the study. "Based on these results, we designed compounds that, even in small amounts, significantly improve disease-associated defects in treated cells."

Myotonic dystrophy type 2 is a relatively rare form of muscular dystrophy that is somewhat milder than myotonic dystrophy type 1, the most common adult-onset form of the disease.

Both types of myotonic dystrophy are inherited disorders that involve progressive muscle wasting and weakness, and both are caused by a type of genetic defect known as a "RNA repeat expansion," a series of nucleotides repeated more times than normal in an individual's genetic code. The repeat binds to the protein MBNL1, rendering it inactive and resulting in RNA splicing abnormalitieswhich lead to the disease.

Many other researchers had tried to find the atomic-level structure of the myotonic dystrophy 2 repeat, but had run into technical difficulties. In a technique called X-ray crystallography, which is used to find detailed structural information, scientists manipulate a molecule so that a crystal forms. This crystal is then placed in a beam of X-rays, which diffract when they strike the atoms in the crystal. Based on the pattern of diffraction, scientists can then reconstruct the shape of the original molecule.

Prior to the new research, which was published in an advance, online issue of the journal ACS Chemical Biology, scientists had not been able to crystallize the problematic RNA. The Scripps Florida team spent several years on the problem and succeeded in engineering the RNA to have crystal contacts in different positions. This allowed the RNA to be crystallizedand its structure to be revealed.

Using information about the RNA's structure and movement, the scientists were able to design molecules to improve RNA function.

The new findings were confirmed using sophisticated computational models that show precisely how the small molecules interact with and alter the RNA structure over time. Those predictive models matched what the scientists found in the studythat these new compounds bind to the repeat structure in a predictable and easily reproducible way, attacking the cause of the disease.

"We used a bottom-up approach, by first understanding how the small components of the RNA structure interact with small molecules," said Jessica Childs-Disney of TSRI, who was first author of the paper with Ilyas Yildirim of Northwestern University. "The fact that our compounds improve the defects shows that our unconventional approach works."


'/>"/>

Contact: Eric Sauter
esauter@scripps.edu
267-337-3859
Scripps Research Institute
Source:Eurekalert  

Related biology news :

1. Scientists look to tackle bacterium that is major cause of diarrhea, vomiting
2. Study led by NUS scientists provides new insights into cause of human neurodegenerative disease
3. Scientists find a groovy way to influence specialization of stem cells
4. WSU scientists find burglary-ring-like mechanism in lethal Contagion virus
5. UCLA stem cell scientists first to track joint cartilage development in humans
6. Sniffing out danger: Rutgers scientists say fearful memories can trigger heightened sense of smell
7. Scientists map food security and self-provision of major cities
8. Scientists identified T372R mutation as potential target for diagnosis and treatment of insulinoma
9. Gene-silencing data now publicly available to help scientists better understand disease
10. Eurofins scientists discover genetic differences between identical twins
11. Oregon scientists offer new insights on controlling nanoparticle stability
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Scientists uncover image of muscular dystrophy defect & design targeted drug candidates
(Date:1/21/2016)... India , January 21, 2016 ... According to a new market research report "Emotion Detection ... and Others), Software Tools (Facial Expression, Voice Recognition ... Regions - Global forecast to 2020", published by ... is expected to reach USD 22.65 Billion by ...
(Date:1/15/2016)... , Jan. 15, 2016 Recent publicized ... small to find new ways to ensure data security ... iOS and Android that ties ... biometrics, transforming it into a hardware authorization token. Customer ... swipe their fingerprint on their KodeKey enabled device to ...
(Date:1/8/2016)... and MANCHESTER, United Kingdom , ... a developer of innovative sensor-based diagnostic products, today announced the ... by new and existing investors.  Proceeds from the financing will ... Scanner , a hand-held device for detecting early-stage pressure ulcers. ... Ireland after receiving CE Mark approval. The ...
Breaking Biology News(10 mins):
(Date:2/5/2016)... -- Amarantus BioScience Holdings, Inc. ... products for Regenerative Medicine, Neurology and Orphan Diseases, announced ... from the US Food and Drug Administration (FDA) for ... granted orphan drug designation (ODD) by the US FDA ... Inc. (OTCQB: AMBS), a biotechnology company ...
(Date:2/4/2016)... -- Sangamo BioSciences, Inc. (NASDAQ: SGMO ), the leader ... Lanphier , Sangamo,s president and chief executive officer, will ... Therapeutic ® development programs and an overview of ... Thursday, February 11, 2016, at the Leerink Partners 5 ... being held in New York . ...
(Date:2/4/2016)... 2016  CytoSorbents Corporation (NASDAQ: CTSO ), ... CytoSorb® blood filter to treat deadly inflammation in ... announced that CEO Dr. Phillip Chan , ... Group,s 2016 Disruptive Growth & Healthcare Conference, providing ... Conference Presentation Details: Where: Convene Conference ...
(Date:2/4/2016)...  Spherix Incorporated (Nasdaq: SPEX ) -- an intellectual property ... intellectual property, today provided an update on the Company,s ... of Texas and announcing that ... Partes Re-examination ("IPR") proceedings that VTech and Uniden ... initiated on only certain claims of two of the ...
Breaking Biology Technology: