The article, titled 'A Model for Neural Development and Treatment of Rett Syndrome Using Human Induced Pluripotent Stem Cells,' describes how the team used a newly-devised procedure to reprogram the skins cells - literally winding back their developmental clock to an earlier state and transforming them into stem cells.
The researchers then employed a second novel technique, taking the newly-formed stem cells and driving them along a developmental path to form nerve cells. When Dr. Muotri and his team examined these new nerve cells closely, they observed characteristic hallmarks of nerve cells with Rett syndrome, including fewer synapses, smaller cell bodies and changes in the cells' signaling capabilities. The group then took their work a step further; testing several drugs previously shown to be effective in mouse models of Rett syndrome, they provided evidence of functional rescue, using human cells. In 1999, the laboratory of Dr. Huda Zoghbi at Baylor College of Medicine, made a seminal discovery, identifying a causative link between mutations in the gene methyl-CpG-binding protein 2 (MeCP2) and Rett syndrome.
This led to further work showing the MeCP2 protein is critical for the proper functioning of nerve cells. In 2007 another study in the laboratory of Dr. Adrian Bird at the University of Edinburgh, Scotland showed that restoration of MeCP2 function in a mouse model of the disease reverses the neurological symptoms in adult mice. This finding provided a critical proof of concept that symptoms of the disorder may be reversible in humans. However, to date, no effective pharmacological treatments have been developed.
The main limitation for human studies and thus, drug development, has been the inaccessibility of live neurons from human patients. To get around this issue, the use of induced pluripotent stem cells (iPSCs) to establish a human cell-based model of Rett syndrome is key to the development of high throughput drug screens and therefore has been an area of the highest priority for IRSF who provided a post-doctoral fellowship Award to Dr. Cassiano Carromeu, a member of the team and a co-author of the current study. The study's principal author, Dr. Alysson Muotri, said, "Dr. Bird's data shows that you can reverse symptoms in a mouse model, now we've shown that this could be done using human cells." "I think the future is to push this in a high throughput screening platform to develop new drugs," he continued.
IRSF recently provided funding to support a new program for Rett syndrome-specific drug development, titled the "Selected Molecular Agents for Rett Therapeutics" (SMART) Initiative. The SMART Initiative will assemble a collection of brain-specific drugs that target select biological mechanisms important in RTT and make the compound collection available to researchers worldwide. IRSF's Chief Scientific Officer, Dr. Antony Horton said "IRSF has been proactive in moving iPSC technology forward for the purpose of drug screening, which is aligned well with the new SMART Initiative." "With the publication of this study, a major hurdle has been overcome in our quest to develop and test new medicines for the benefit of people living with Rett syndrome." added Dr. Horton.
About Rett Syndrome (RTT)
Rett syndrome is a developmental neurological disorder, occurs almost exclusively in females. RTT results in severe movement and communication problems following apparently normal development for the first six months of life. Characteristic features of the disease include loss of speech and purposeful hand use, repetitive hand movements, abnormal walking, abnormal breathing, slowing in the rate of head growth and increased risk of seizures. Current treatment for girls with RTT includes physical and occupational therapy, speech therapy, and medication for seizures. There is no known cure for RTT. In 2007, researchers heralded a major breakthrough by reversing RTT symptoms in mouse models. RTT is considered a "Rosetta Stone" that is helping scientists understand multiple developmental neurological disorders, and shares genetic links with other conditions such as autism and schizophrenia.
About the International Rett Syndrome Foundation
IRSF is the world's leading private funder of basic, translational and clinical Rett syndrome research, funding over $24M in high-quality, peer-reviewed research grants and programs to date. Annually, IRSF hosts the world's largest gathering of global Rett researchers and clinicians to establish research direction and priorities while exchanging ideas and the most recent information. IRSF is the most comprehensive non-profit organization dedicated to providing thorough and accurate information about Rett syndrome, offering informational and emotional family support, and stimulating research aimed at accelerating treatments and a cure for Rett syndrome and related disorders. IRSF has earned Charity Navigator's most prestigious 4 star rating. To learn more about IRSF and Rett syndrome, visit www.rettsyndrome.org or call IRSF at 1-800-818-RETT (7388).
About the University of California, San Diego
Founded in 1960, the University of California, San Diego is one of the nation's most accomplished research universities, widely acknowledged for its local impact, national influence and global reach. UC San Diego is renowned for its collaborative, diverse and cross-disciplinary ethos that transcends traditional boundaries in science, arts and the humanities. The university's award-winning scholars are experts at the forefront of their fields with an impressive track record for achieving scientific, medical and technological breakthroughs. A leader in climate science research, UC San Diego is one of the greenest universities in the nation and promotes sustainability solutions throughout the region and the world. http://www.ucsd.edu
Stephen Bajardi | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences