Imagining Gene Therapy For Girls With Rare Rett Syndrome

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Guest Contributor

Imagine your daughter has a debilitating genetic disease — a disorder that will plague her for the rest of her life. Now imagine hearing about a treatment that might improve her condition dramatically.


That the kind of brimming-with-hope feeling many parents had six years ago when Scottish researcher Adrian Bird announced that he had reversed a genetic condition called Rett Syndrome in adult mice.

Of course everyone who heard about the study understood that curing a mouse is not the same as helping a person, but the improvements stunned researchers who had assumed that a mouse would never be able to recover from the restricted mobility, tremors and unusual brain activity that characterize the mouse version of the disease.

The parents of girls with Rett Syndrome – which occurs mainly in females, because males with the genetic mutation usually die before birth – suddenly had hope that their children might someday be able to talk, run, wave or blow them a kiss.

Girls with Rett, which affects about 16,000 Americans and 340,000 worldwide, are born apparently normal but regress between 6 and 18 months of age when their brain development stalls, and they are left with severe movement limitations and communication deficits.

But the way Bird, a professor of genetics at Edinburgh University, cured the mice wasn’t feasible in people,  so all they could do was wait and hope.

Today, Bird and colleagues published another study in The Journal of Neuroscience, showing a treatment for adult, female mice that might someday be usable in people. (The study isn’t online yet, but the press release has more information and an interview with collaborators.)

He and collaborators at Oregon Health and Science University and elsewhere showed that by infecting the female mice with a specially designed virus, they could make up for the loss of the MECP2 gene, which Bird discovered in 1990 was missing in Rett Syndrome.

There has always been some hope for Rett Syndrome girls, because their brain cells aren’t killed by the genetic mutation – they’re just effectively turned off by the lack of a protein made by the MECP2 gene. Deliver that protein to as many cells as possible, and you can restore the functions, the mouse research suggests.

But gene therapy has had a rocky history over the last 15 years, and is only now becoming a viable treatment. (Here's a strong piece by Carl Zimmer in Wired that delves into the history and current state of gene therapy.)

The new treatment is delivered on the back of a virus altered so it cannot cause illness – but can deliver the MECP2 protein. The researchers chose a virus that can pass into the brain and has been shown to infect both nerve cells and other brain cells, which are known to be affected by Rett. The virus, AAV9, also lives on in cells that don’t divide – like nerve cells – which researchers hope will be helpful for making any improvements permanent.

Unfortunately, the virus is too small to carry the whole MECP2 gene, so researchers had to pick and choose segments they thought were the most important. (The virus was administered to the mice via three shots in the brain – ouch! A later version was delivered in the veins and seemed to work too.) 

Of course the research is still in early days and will need to be tweaked significantly before being tried in people.

Karen Weintraub, a Cambridge-base health/science journalist, is a frequent contributor to CommonHealth. Follow her on Twitter @kweintraub.

This program aired on August 20, 2013. The audio for this program is not available.



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