Rett syndrome is a rare genetic condition that predominately affects women, with around one in every 10,000 girls diagnosed with it. The condition is a neurological disorder that stops the nerve cells in the brain from developing properly, and will often go unnoticed by parents at the beginning, with symptoms generally starting to develop when the child reaches a few months old.
Rett Syndrome has been labeled by some as an autism spectrum disorder (ASD), as it has some similarities, although the link between the two has been contested.
Now, researchers think that they may have developed an experimental drug treatment, which has been shown to improve symptoms in mice that also have Rett syndrome. “At this time, there is no disease-modifying therapy for Rett syndrome,” said Professor Nicholas Tonks, who carried out the research at Cold Spring Harbor Laboratory, “and the focus of most current therapies is management of symptoms. Our approach represents a new strategy.”
The condition is what’s called an X-linked disorder. This means that it is a genetic mutation, specifically of the MECP2 gene, that occurs on the X chromosome. In almost all cases, the mutation is sporadic, and occurs without any family history of the condition. Men have one copy of the X chromosome, and one Y, whereas women have two X chromosomes. This means that if a male has the mutation on the X chromosome, there is no healthy copy of the gene on the Y to fall back on. This is why most males born with the mutation die soon after birth.
With women, however, they do have a healthy version on their other X chromosome, which can compensate to a certain degree for the faulty gene. But, while they might survive, they are still neurologically impaired. The symptoms of the condition develop with age, and include slowness in development, abnormal hand movements, unsteadiness when walking, seizures, and spasticity. There is currently no cure and most sufferers will be dependent on 24-hour care for their entire lives.
The new research, however, published in The Journal of Clinical Investigation, has shown how inhibiting a particular enzyme, PTP1B, was able to improve the symptoms in behavioral tests of mice bred to express the mutation. They found that there was a link between this enzyme and a neural growth factor (a protein that controls the development of nerve cells). Under normal conditions, the enzyme levels are low, allowing the growth factor to signal and so nerve cells to develop normally. With Rett syndrome, though, the levels of the enzyme are much higher and interferes with the growth factor, meaning the development of nerve cells is stunted. By inhibiting the enzyme and allowing the development to occur normally, they found improvements in the behavior of the mice.
“In the research we’re reporting today, we have clear evidence in mice that we can actually reverse symptoms – supporting the concept that the disorder is not irreversible and may be amenable to treatment with small molecule drugs,” explained Tonks.