Expression of a toxic RNA that leads to Fragile X Tremor Ataxia Syndrome is modifiable by genetic or pharmacologic means, according to new research from U-M Medical School scientists.
In the study published online today in the journal Public Library Of Science Genetics, U-M's Peter K. Todd, M.D., Ph.D., led a team of researchers who examined the expression of a toxic messenger RNA (mRNA) seen in the brains of those afflicted with the syndrome.
Fragile X Tremor Ataxia Syndrome (FXTAS) is usually found in older adults, who often have grandchildren afflicted with Fragile X. Those affected with the adult form of the syndrome have slow gait, tremors, dementia and balance problems. The symptoms are caused by overproduction of a toxic mRNA in the brain that causes neurodegeneration.
"We found that the expression of this toxic mRNA is dynamic and modifiable," says Todd, who is an assistant professor in U-M's Department of Neurology. "There is a potential for modifying the increased production of the toxic RNA with drugs that inhibit histone acetylation."
FXTAS is an under-diagnosed syndrome that was only discovered about 10 years ago, when researchers discovered the grandfathers of children with Fragile X were displaying common symptoms. It is one of three known Fragile X disorders that result from changes in the Fragile X gene. The altered gene can be passed down through generations, affecting both genders at different stages in life.
About 1 in 3,000 men and about 1 in 5,200 women in the general population will develop symptoms of FXTAS, according to the National Fragile X Foundation. Current estimates suggest that about 30-40 percent of male Fragile X gene carriers over 50 years of age, within families already known to have someone with a Fragile X-associated disorder, will ultimately exhibit some features of FXTAS.
Fragile X is the most common cause of developmental delay in boys and is the most common known single gene cause of autism.
Using both fruit fly models and human cells, the U-M researchers found that drugs that inhibit histone acetyltransferases modify the brain changes associated with FXTAS and could provide the pathway to a therapeutic target.
"These drugs that we used are too toxic for use in patients but the important finding is that we have a better idea of what's driving this syndrome and proof of principle that those brain changes can be modified," says Todd.
"Our findings underscore the need for developing more specific modifiers of expression at the Fragile X gene, with the long-term goal of developing preventive therapy for FXTAS patients," says Todd.
Todd stressed the need for more research into neurodegenerative diseases like FXTAS, which can be devastating to families.
"This should be a high priority. Neurodegeneration robs people of their humanity," Todd says. "To lead a happy and fruitful life, you have to protect the brain."
Journal reference: PLoS Genetics, 6(12): e1001240. doi:10.1371/journal.pgen.1001240
Funding: AAN Foundation award, National Institutes of Health, Harris Professorship to Peter K. Todd.
Additional authors: Henry L. Paulson, professor U-M's Department of Neurology; Seok Yoon Oh and Amy Krans, U-M Department of Neurology; Udai B. Pandey, Louisiana State University Health Sciences Center; Nicholas DiProspero, Johnson & Johnson; Kyung-Tai Min, University of Indiana; J. Paul Taylor, St. Jude's Children's Hospital.
About the University of Michigan's Department of Neurology: The department is an academic medical department with a full range of activities in patient care, education and research. The Neurology inpatient service provides care for acutely ill patients with neurologic disease and includes a dedicated intensive care unit, a separate stroke unit, and inpatient epilepsy monitoring beds. Our faculty also investigate the causes, treatments, natural history and phenotypic spectrum of inherited neurologic disorders, such as Alzheimer's disease. Our studies range from describing novel inherited neurologic syndromes; to family studies including genetic mapping ; discovering genes for neurologic diseases; and the creation and analysis of laboratory animals of neurologic disease.
Mary F. Masson | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy