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Reactivating MECP2 Consortium

There is no mystery about why a girl suffers from Rett Syndrome. The cause is the mutated copy of the MECP2 gene inhabiting her cells. But since MECP2 is on the X chromosome and all females have two X’s, beside each active mutated gene rests a healthy but silenced twin. What if we could mitigate the flawed gene by reawakening its silenced counterpart? If we could wake up MECP2 in enough cells we could conceivably reverse Rett symptoms.

Because there is a healthy copy of the gene in every cell, we don’t have to deliver it, it’s already there, we just have to find a way to wake it up … it’s a very attractive approach and one that RSRT has championed since our launch in 2008.


We are currently funding a number of labs that are pursuing this line of work. At the University of North Carolina at Chapel Hill we are supporting a collaboration between Benjamin Philpot, Bryan Roth and Terry Magnuson; Jeannie Lee at Harvard; Antonio Bedalov at the Fred Hutchinson Cancer Research Institute; and Joost Gribnau at Erasmus MC in the Netherlands.

You may ask why do we need multiple labs working on the same goal. Isn’t that a waste of effort and money? The answer is a resounding “NO”. While the end game is the same each lab is using a different strategy to get there.

Our MECP2 reactivation consortium has been another bright spot in the work that we do with the RSRT. Our consortium consists of laboratories from all over the US and abroad. We share the goal and urgency of bringing much needed treatment to patients. The level of sharing and the resulting progress towards reactivating the silent copy of MECP2 are heartening to see. The consortium is making a real difference.


Harvard Medical School

Why it Works

For example, the types of cells that labs are utilizing are different. Ben Philpot and colleagues at UNC are working with mouse neurons, Toni Bedalov and Jeannie Lee are using fibroblast cells, others are using human cells. Each cell type has its own set of advantages and disadvantages.

The labs are also using different “reporters” – meaning how the cells are designed to detect activation of MECP2. Different compound libraries at different concentrations are being screened. Compounds are also being screened at various degrees of high and low throughput.

Unlike the MECP2 Consortium and Gene Therapy Consortium this group of researchers did not start out as a consortium. However through conference calls and in person meetings this group of researchers has evolved into an effective and productive collaboration.

One immediate advantage of the consortium approach is that discoveries in any of the labs can rapidly be validated in the other labs.

Current Projects