Encouraging development in healing a genetic related condition

February 9, 2007

Press Release

Media Contact:

Coenraads

Director of Research, RSRF

monica@...

EMBARGOED UNTIL FEBRUARY 8, 2007 2 p.m. U.S. EASTERN TIME

REVERSAL OF SYMPTOMS IN AN AUTISM SPECTRUM DISORDER

Rett Syndrome is reversed in genetic mouse model

Cincinnati, OH (February 8, 2007) -The Rett Syndrome Research Foundation

(RSRF) announces results of a landmark study reversing the symptoms of Rett

Syndrome (RTT) in a genetic mouse model. The findings, by Bird, Ph.D., of

the University of Edinburgh and Chairman of the RSRF Scientific Advisory Board,

appear online in Science Express on February 8, 2007. Rett Syndrome is a severe

childhood neurological disease that is the most physically disabling of the

autism spectrum disorders. The experiments were funded by the Rett Syndrome

Research Foundation (RSRF), the Wellcome Trust and the Rett Syndrome U.K./Jeans

for Genes.

Caused by mutations in the gene MECP2, RTT affects primarily girls,

striking at random in early childhood and destroying speech, normal movement and

functional hand use. Many children become wheelchair bound; those who walk

display an abnormal, stiff-legged gait. Disordered breathing patterns and

Parkinson-like tremors are common.

Restoration of fully functional MECP2 over a four week period eradicated

tremors and normalized breathing, mobility and gait in mice that had previously

been fully symptomatic and, in some cases, only days away from death.

" Like many other people, we expected that giving MECP2 to mice that were

already sick would not work, " said Bird. " The idea that you could put back an

essential component after the damage to the brain is done and recover an

apparently normal mouse seemed farfetched, as nerve cells that developed in the

absence of a key component were assumed to be irrevocably damaged. The results

are gratifyingly clear, though, and must give hope to those who are affected by

this distressing disorder. "

Bird is Buchanan Professor of Genetics at University of Edinburgh and

Director of the Wellcome Trust Centre for Cell Biology. MECP2, first identified

by Bird in 1990, is considered to be a protein that regulates the expression of

other genes by turning them off at the appropriate time.

In 1999 Huda Zoghbi, M.D., Professor, Departments of Molecular and Human

Genetics, Pediatrics, Neurology, and Neuroscience at Baylor College of Medicine

discovered that RTT is caused by mutations in the MECP2 gene. Mutations in MECP2

are now being seen in some cases of childhood schizophrenia, classic autism and

learning disabilities. " The findings are extraordinary, and are of relevance not

only to Rett Syndrome but to a much broader class of disorders, including autism

and schizophrenia. The successful restoration of normal function demonstrated in

the mouse models suggests that if we can develop therapies to address the loss

of MECP2 we may be able to reverse neurological damage in children and adults

with Rett, autism and related neuropsychiatric disorders, " commented Zoghbi.

The reversal experiments were carried out in the Bird lab by research

assistant Jacky Guy. Employing technology known as Cre-lox recombination, she

created mouse models in which MECP2 was silenced by insertion of a Stop cassette

into the gene, resulting in the neurological deficits seen in RTT. Silencing

could be reversed at will by removing the Stop cassette, thereby reactivating

the MECP2 gene. This was achieved by treating the mice with a drug that caused

the enzyme Cre to enter the cell nucleus where it could splice out the cassette.

As well as losing overt behavioral defects, the mice also recovered a key

electrophysiological function of the brain. This was determined by measuring LTP

(long-term potentiation) which provides a quantifiable measurement of the

ability of neurons to respond to stimulation. LTP has long been thought to

reflect the cellular basis of learning and memory. Though LTP in RTT mice models

was defective, it was restored to normal function by the reversal experiments.

" The reversal of neurological defects, reported in the remarkable article

by Guy et al, is surprising because the cause of the symptoms occurred early in

development and was expected to be permanent. Of particular note is the recovery

of LTP, which is the best current physiological correlate of learning and

memory. These findings are very encouraging for those searching for a treatment

because they give hope that the symptoms could not only be halted from

progressing, but the course of the disease itself may be able to be reversed, "

stated Fred Gage, Ph.D. of the Salk Institute of Biological Studies.

" Dr. Bird's astonishing results usher in a new era for Rett Syndrome and

other autism spectrum disorders. The reversal experiments provide justification

for aggressive exploration of next steps on all fronts, from drug discovery to

gene correction. The Rett Syndrome Research Foundation will be focused on a

comprehensive effort to identify and speed treatments to the children and adults

in dire need of them, " commented Coenraads, co-founder and Director of

Research for RSRF and mother of a young daughter with the disorder.

About the Rett Syndrome Research Foundation

The Rett Syndrome Research Foundation (www.rsrf.org) was created in late

1999 and is the largest private source of funds for biomedical research on Rett

Syndrome.

About the Wellcome Trust

The Wellcome Trust is the largest charity in the UK and the second largest

medical research charity in the world. It funds innovative biomedical research,

in the UK and internationally, spending around £500 million each year to support

the brightest scientists with the best ideas. The Wellcome Trust supports public

debate about biomedical research and its impact on health and wellbeing.

www.wellcome.ac.uk

February 9, 2007

oh my gosh - this is breathtakingly amazing~! wouldn't it be amazing???

love,

yuka

Encouraging development in healing a genetic related

condition