Research breakthrough hailed on the anniversary of gene discovery

In a study published today in the Journal, Proceedings of the National Academy of Sciences, an international team of researchers based in the U.S. and UK revealed that they were able to halt the potentially lethal, breath holding episodes associated with the neurological disease Rett syndrome. Rett syndrome is a disorder of the brain that affects around 1 in 10,000 young girls. On October 4, 1999, a groundbreaking study was published showing that the disease is caused by a spontaneous mutation in the gene methyl-CpG-binding protein 2 (MeCP2). The gene encodes a protein which acts as a "master switch" that is critical for controlling the expression of many other genes regulating the production of specific proteins in brain cells.

One of the more serious consequences of the disease is the intermittent episodes of breath holding, which can put individuals at risk for brain damage due to oxygen deprivation. The team led by Professor John Bissonnette, M.D., of Oregon Health and Science University, Portland OR and Professor Julian FR Paton, PhD, at the University of Bristol in the UK discovered a way to prevent the frequent episodes of breath holding in a mouse model of Rett syndrome using a unique combination of drugs.

Initially, the investigators' earlier work found that an area of the brain that allows breathing to persist throughout life, without interruption, has reduced levels of a vital transmitter substance called gamma-aminobutyric acid (GABA). The researchers took a two-pronged approach, using one set of drugs to increase the amount of GABA, and others to target a specific type of serotonin receptor to reduce activity in brain cells that normally depress inhalation. Both of these approaches halted the life threatening episodes of breathing arrests in Rett syndrome mice and confirmed the investigators' initial theory.

Dr. Bissonnette, co-principal investigator on the IRSF funded study commented, "When the phrenic nerve going to the diaphragm is silent, nerves going to muscles for expiration are excessively active. Building on our earlier studies that showed a defect in inhibition within the brain's respiratory areas, we reasoned that expiratory neurons were not receiving enough inhibition. When we boosted inhibition, or separately used a drug known to silence expiratory neurons, the pattern of breath holding was markedly improved." Dr. Bissonnette added, "While the specific drugs used in this mouse study are not available for human use, drugs with similar modes of action have been used in other conditions."

On Friday, the International Rett Syndrome Foundation (IRSF) announced $1.5M in funding for new research grants in 2010. IRSF announced continuing support for Drs. Bissonnette and Paton who will conduct follow-up studies to further investigate the pharmacological treatment of respiratory dysfunction in mouse models of Rett syndrome.

Commenting on the study, IRSF Chief Scientific Officer Dr. Antony Horton said, "The work of Drs. Bissonnette and Paton presents a powerful proof of concept which allows us to think of new ways to potentially treat this life-threatening complication of Rett syndrome. Their newly-funded studies, demonstrate our continued commitment towards advancing new therapeutic strategies to treat and ultimately reverse this devastating disease."

Source: International Rett Syndrome Foundation