Developmental disease is recreated in an adult model

June 02, 2011

(Cincinnati, OH) - An IRSF funded study published today in the journal Science has shown that the childhood disorder Rett syndrome, can be reestablished in adult animals by "switching off" a critical disease causing gene in healthy adult animals. The gene was "switched off" in adult mice by use of a sophisticated genetic trick, resulting in the appearance of behaviors typically seen in Rett syndrome. The leading author Christopher McGraw, MD/PhD student, carried out the study in the laboratory of Dr. Huda Zoghbi, a renowned neuroscientist based at Baylor College of Medicine, and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital in Houston TX.

In 1999 Dr. Zoghbi's laboratory made a central discovery, identifying the causative link between mutations in the gene methyl-CpG-binding protein 2 (MeCP2) and Rett syndrome. This work led to other studies showing that MeCP2 protein is critical for the proper functioning of nerve cells during development and into adulthood. In 2007 a further study conducted by Dr. Adrian Bird, at Edinburgh University in the UK, showed the neurological symptoms of Rett syndrome can be reversed by reactivating MeCP2 in an adult mouse where the disease is already established. This work provided a critical proof of concept that symptoms of the disorder may be reversible in humans; however, to-date it was not known whether the early developmental period was important in establishing the course of the disease. This new study argues that early expression of the gene does not protect against the development of symptoms if the disease gene is later inactivated.

Commenting on the study, Dr. Zoghbi said "We did this experiment to see if providing MeCP2 early on in life, during critical periods of brain maturation, would be partially protective from loss of this protein in the adult brain. We were surprised to see that the nervous system had no detectable protection when MeCP2 was lost in adulthood. This affirmed that brain cells must have MeCP2 at all times to function normally."

There have been no effective pharmacological treatments developed to treat the disorder although new therapeutic trials are currently underway. This work suggests that therapies for Rett syndrome may need to be continuously maintained throughout the course of an individual's life.
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Funding for this work was jointly provided by the National Institutes of Health, the Baylor College of Medicine Research Advocates for Student Scientists, the International Rett Syndrome Foundation (www.rettsyndrome.org), the Simons Foundation and the Rett Syndrome Research Trust.

About Rett Syndrome

Rett syndrome (RTT), 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 to 18 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 Baylor College of Medicine

Baylor College of Medicine (www.bcm.edu) in Houston is recognized as a premier academic health science center and is known for excellence in education, research and patient care. It is the only private medical school in the greater southwest and is ranked as one of the top 25 medical schools for research in U.S. News & World Report. BCM is listed 13th among all U.S. medical schools for National Institutes of Health funding, and No. 2 in the nation in federal funding for research and development in the biological sciences at universities and colleges by the National Science Foundation. Located in the Texas Medical Center, BCM has affiliations with eight teaching hospitals. Currently, BCM trains more than 3,000 medical, graduate, nurse anesthesia, and physician assistant students, as well as residents and post-doctoral fellows. BCM is also home to the Baylor Clinic, an adult clinical practice that includes advanced technologies for faster, more accurate diagnosis and treatment, access to the latest clinical trials and discoveries, and groundbreaking healthcare based on proven research. Follow Baylor College of Medicine on Facebook (www.facebook.com/BaylorCollegeOfMedicine) and twitter (http://twitter.com/BCMHouston).

International Rett Syndrome Foundation

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