Adrian Bird
In 2007, the Bird lab published the dramatic reversal experiments in fully adult male and female mice.This surprising and unexpected result suggests that Rett Syndrome is a reversible disorder. The following experiments are now underway in the Bird lab.
Detailed analysis of Reversal Phenotypes
Behavioural, cognitive and social analysis is being undertaken in both Rett mice and reversed mice to determine the exact degree of reversal.
Fragile X and Rett:
Like Rett, Fragile X is a disorder caused by mutations in one gene (Fmr1). When that gene is mutated, protein synthesis fails to shut down, leading to an excess of protein. Some years ago, Mark Bear of MIT proposed that antagonists of the glutamate receptor mGluR5 might counteract over expression of that protein and therefore cancel out the damaging effects of Fmr1 deficiency. Current clinical trials of mGluR5 antagonists look promising.
Bear has proposed that just as Fragile X is due to over-synthesis of proteins at the synapse, Rett may be due to under-expression of protein at the same locations. In cooperation with Bear, the Bird lab will test this hypothesis.
A search for molecular chaperones for MeCP2 (T158M)
Previous work from the Bird lab suggests that the T158M mutation (the most common mutation) disrupts the natural folding that occurs at this particular amino acid position in the MeCP2 protein. In this project the researchers will try to identify small molecules which will counteract the misfolding. The hope is that restoring proper folding will improve symptoms of the disorder.
Approaches to gene therapy
In collaboration with gene therapist, Ronald Crystal at Weill Cornell, the Bird lab will test the ability of the AAVrh10vector to spread throughout the brain and ameliorate Rett symptoms.
RSRT UK funds delivered to this collaborative project in 2010: £22,600
RSRT UK funds delivered to this collaborative project in 2011: £6250
June 2011 £12,510
Total RSRT UK funding to date: £41,360