Navigation Links
Excess DNA damage found in cells of patients with Friedreich's ataxia
Date:1/14/2010

PITTSBURGH, Jan. 14 Elevated levels of DNA damage have for the first time been found in the cellular mitochondria and nuclei of patients with the inherited, progressive nervous system disease called Friedreich's ataxia (FRDA), says a multicenter research team led by an expert from the University of Pittsburgh Cancer Institute (UPCI). The findings, described today in PLoS Genetics, shed light on the molecular abnormalities that lead to the disease, as well as point the way to new therapeutic approaches and the development of biomarker blood tests to track its progression.

"In FRDA, mutations in the gene frataxin reduce production of a protein that plays a role in keeping iron levels in balance within mitochondria," explained Bennett Van Houten, Ph.D., Richard M. Cyert Professor of Molecular Oncology and leader of the molecular and cellular cancer biology program at UPCI, and professor, Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine. "Frataxin binds iron and helps build iron-sulfur clusters, which are important constituents of cellular proteins."

"While iron is what allows blood cells to carry oxygen, too much iron is toxic to the body," said Astrid C. Haugen, lead author and program analyst at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health (NIH). "Friedreich's ataxia leads to iron overload, setting the stage for cumulative DNA damage that eventually affects patients' nerve and muscle cells."

According to the National Institute of Neurological Disorders and Stroke (NINDS), about 1 out of 50,000 Americans has Friedreich's ataxia. Symptoms appear from 5 to 15 years of age and include ataxia, or gait disturbance, that results from degeneration of nerves in the spinal cord and muscle; muscle wasting; and speech problems. Heart enlargement, arrhythmias, and heart failure are common and often the cause of early death in the most severely affected. Patients typically require wheelchairs within 10 to 20 years after symptoms begin.

For the study, the researchers profiled gene activity in blood samples from FRDA children to search for biomarkers of the disease, as compared to young healthy donors. Those data were compared to blood tests from FRDA adults, and the latter compared to a second group of healthy individuals.

"We saw gene activity patterns that are associated with responses to DNA damage, and our comparisons and follow-up tests showed us that FRDA patients have far more damage than seen in healthy people," said Dr. Van Houten, who noted that everyone has some DNA damage, at various stages of repair, in their cells. "We found gene expression signatures that correlated with frataxin levels, age of disease onset and a standardized measure of patient disability."

"If further testing validates the set of genes and activity profiles as predictive biomarkers, they could be useful in assessing the current status of a patient's illness as well as the response to experimental therapies in clinical trials," he said. "Also, new drug targets might be found in the DNA repair and iron-processing pathways affected by the lack of frataxin, generating much-needed treatment breakthroughs."


'/>"/>

Contact: Anita Srikameswaran
SrikamAV@upmc.edu
412-578-9193
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

Related biology news :

1. Vitamin B-12 function may be diminished by excessive folate
2. Diabetes linked to male infertility; excess sugars in the body have direct effect on sperm quality
3. Low sperm count may be associated with prenatal testosterone excess
4. Diatom genome helps explain success in trapping excess carbon in oceans
5. Study: Excessive use of antiviral drugs could aid deadly flu
6. UTMB study identifies women at risk of gaining excessive weight with injectable birth control
7. New study finds way to stop excessive bone growth following trauma or surgery
8. Human derived stem cells can repair rat hearts damaged by heart attack
9. Enzyme alerts cells powerful army to repair DNA damage
10. Simulation reveals how body repairs balance after damage
11. Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/3/2016)... 3, 2016 Das ... Nepal hat ein 44 ... geprägter Kennzeichen, einschließlich Personalisierung, Registrierung und IT-Infrastruktur, ... Produktion und Implementierung von Identitätsmanagementlösungen. Zahlreiche renommierte ... Januar teilgenommen, aber Decatur wurde als konformste ...
(Date:6/2/2016)... Perimeter Surveillance & Detection Systems, ... Infrastructure, Support & Other Service  The latest ... comprehensive analysis of the global Border Security market ... of $17.98 billion in 2016. Now: In ... in software and hardware technologies for advanced video surveillance. ...
(Date:5/20/2016)... 2016  VoiceIt is excited to announce its ... By working together, VoiceIt and VoicePass will ... VoicePass take slightly different approaches to voice biometrics, ... and usability. ... partnership. "This marketing and technology partnership ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... 27, 2016  Global demand for enzymes is ... 2020 to $7.2 billion.  This market includes enzymes ... products, biofuel production, animal feed, and other markets) ... biocatalysts). Food and beverages will remain the largest ... consumption of products containing enzymes in developing regions.  ...
(Date:6/27/2016)... ... June 27, 2016 , ... Newly ... technologies, services and solutions to the healthcare market. The company's primary focus is ... manufacturing, sales and marketing strategies that are necessary to help companies efficiently bring ...
(Date:6/24/2016)... , June 24, 2016 Epic ... sensitively detects cancers susceptible to PARP inhibitors by ... tumor cells (CTCs). The new test has already ... therapeutics in multiple cancer types. Over ... DNA damage response pathways, including PARP, ATM, ATR, ...
(Date:6/23/2016)... , June 23, 2016   Boston ... of novel compounds designed to target cancer stemness ... has been granted Orphan Drug Designation from the ... treatment of gastric cancer, including gastroesophageal junction (GEJ) ... inhibitor designed to inhibit cancer stemness pathways by ...
Breaking Biology Technology: