Navigation Links
Drosophila drug screen for fragile X syndrome finds promising compounds and potential drug targets
Date:3/9/2008

Scientists using a new drug screening method in Drosophila (fruit flies), have identified several drugs and small molecules that reverse the features of fragile X syndrome -- a frequent form of mental retardation and one of the leading known causes of autism. The discovery sets the stage for developing new treatments for fragile X syndrome.

The results of the research by lead scientist Stephen Warren, PhD, chair of the Department of Human Genetics at Emory University School of Medicine, are published online in the journal Nature Chemical Biology.

Dr. Warren led an international group of scientists that discovered the FMR1 gene responsible for fragile X syndrome in 1991. Fragile X syndrome is caused by the functional loss of the fragile X mental retardation protein (FMRP). Currently there is no effective drug therapy for fragile X syndrome, and previously no assays had been developed to screen drug candidates for the disorder.

During the past 17 years, intense efforts from many laboratories have uncovered the fundamental basis for fragile X syndrome. Scientists believe FMRP affects learning and memory through regulation of protein synthesis at synapses in the brain. One leading view, proposed by Dr. Warren and colleagues, suggests that over stimulation of neurons by the neurotransmitter glutamate is partly responsible for the brain dysfunction resulting from the loss of FMRP.

In their current experiment, Emory scientists used a Drosophila model lacking the FMR1 gene. These fruit flies have abnormalities in brain architecture and behavior that parallel abnormalities in the human form of fragile X syndrome. When FMR1-deficient fly embryos were fed food containing increased levels of glutamate, they died during development, which is consistent with the theory that the loss of FMR1 results in excess glutamate signaling.

The scientists placed the FMR1-deficient fly embryos in thousands of tiny wells containing food with glutamate. In addition, each well contained one compound from a library of 2,000 drugs and small molecules. Using this screening method, the scientists uncovered nine molecules that reversed the lethal effects of glutamate.

The three top identified compounds were known activators of GABA, a neural pathway already known to inhibit the effects of glutamate. In the study, GABA reversed all the features of fragile X syndrome in the fruit flies, including deficits in the brain's primary learning center and behavioral deficits. The screening also identified other neural pathways that may have a parallel role in fragile X syndrome and could be targets for drug therapy.

"Our discovery of glutamate toxicity in the Drosophila model of fragile X syndrome allowed us to develop this new screen for potential drug targets," notes Dr. Warren. "We believe this is the first chemical genetic screen for fragile X syndrome, and it highlights the general potential of Drosophila screens for drug development.

"Most importantly, it identifies several small molecules that significantly reverse multiple abnormal characteristics of FMR1 deficiency. It also reveals additional pathways and relevant drug targets. These findings open the door to development of effective new therapies for fragile X syndrome."


'/>"/>

Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University
Source:Eurekalert

Related medicine news :

1. MultiVu Video Feed: New National Colorectal Cancer Screening Guidelines Issued by the American Cancer Society
2. ASGE Re-Launches Colon Cancer Awareness Web Site www.Screen4coloncancer.Org for National Colorectal Cancer Awareness Month
3. New guidelines update recommendations on colorectal cancer screening
4. New Guidelines Update Recommendations on Colorectal Cancer Screening
5. Health groups issue updated colorectal cancer screening guidelines
6. A new more effective tuberculosis screening test for HIV victims
7. Screening the herbal pharmacy
8. Renowned Doctor Says Best Way to Obtain Crucial Vitamin D Is From Sun; but Still, Dont Forget Sunscreen
9. Task Force Recommends Against Screening for Chronic Obstructive Pulmonary Disease Using Spirometry
10. In Early Childhood, Continuous Care by One Doctor Improves Delivery of Health Screenings
11. In early childhood, continuous care by 1 doctor improves delivery of health screenings
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:8/16/2017)... Lewisville, TX (PRWEB) , ... August 16, 2017 , ... ... in the United States, named Dr. Douglas J. Harrison, as the new Medical Director ... will be the new facility Medical Director of our Sienna Plantation location,” said Dr. ...
(Date:8/16/2017)... ... , ... “God Will Break Every Chain”: an inspirational story for those shackled by the chains ... author, Evangelist Joann Shivers, a writer and a woman of great faith and wisdom. ... early age. She was born and raised in Vero Beach, Florida and has dedicated ...
(Date:8/15/2017)... ... August 15, 2017 , ... The first study to ... multiple myeloma has been completed, with the team’s findings now published online ahead of ... , Director of the Blood and Marrow Transplant Program at Roswell Park Cancer Institute, ...
(Date:8/15/2017)... ... August 15, 2017 , ... Progressive Dental, a leading ... on the 2017 Fast 50 list of Fastest Growing Companies in Tampa Bay. The ... area who has shown three consecutive years of growth. For this year’s award, Progressive ...
(Date:8/15/2017)... ... August 15, 2017 , ... Dr. Timothy Davis ... periodontal disease . This information can be used to develop patient-specific treatment ... The two salivary diagnostic tests, named MyPerioPath® and MyPerioID® are offered by OralDNA® ...
Breaking Medicine News(10 mins):
(Date:7/28/2017)... Hill-Rom Holdings, Inc. ("Hill-Rom") (NYSE: HRC), today ... June 30, 2017, and updated its financial outlook for ... For the fiscal third quarter, Hill-Rom reported earnings of ... share in the prior-year period. These results reflect after-tax ... share primarily related to the non-cash write-down of assets ...
(Date:7/27/2017)... Pa., July 27, 2017  West Pharmaceutical Services, Inc. ... results for the second-quarter 2017 and updated financial guidance ... Second-Quarter 2017 Highlights Reported net ... over the prior-year quarter. Net sales at constant currency ... reported-diluted EPS was $0.51, compared to $0.60 in the ...
(Date:7/26/2017)... , July 26, 2017 Sancilio Pharmaceuticals Company, ... our clinical trial evaluating Altemia TM , an oral ... and Sickle Cell Disease (SCD). The SCOT Trial, is ... efficacy and safety of Altemia TM in pediatric ... under US IND 125274. ...
Breaking Medicine Technology: