Skip to main content

“Disease in a Dish” Platform Receives a $1 Million Influx from RSRT

April 19, 2016

Alysson Muotri has been working on Rett Syndrome for over a decade, first in the laboratory of his mentor, Fred (Rusty) Gage at the Salk Institute, and now in his own lab at University of California San Diego.

Dr. Muotri is a leader in the field of induced pluripotent cells, (iPS). Through collaborations with clinicians he collects patient cells from skin, blood or sometimes teeth of individuals with a disease. He then coaxes these cells back into an embryonic state where they have the potential to become any type of cell in the body. These cells are called iPS cells. Muotri can then take these iPS cells and turn them into neuronal cells. Simply put he can create brain cells that have a particular disease mutation.

Scientists can study these cells and identify how they differ from normal cells. For example, Rett neurons have fewer synapses, reduced spine density and smaller nucleuses. MECP2 Duplication Syndrome cells, on the other hand, have increased synaptogenesis and dendritic complexity.

Knowing what is wrong allows the possibility of screening for drugs that ideally can fix these problems. Dr. Muotri is establishing relationships with various drug companies that are interested in screening their compound libraries in the platform that he has created.

RSRT has awarded Dr. Muotri $1 million for research on Rett Syndrome and MECP2 Duplication Syndrome.

MECP2 Duplication Syndrome – Award of $792,000

Last year, the Muotri lab generated stem cell-derived “mini-brains” from patients with MECP2 Duplication Syndrome and found a candidate drug, NCH-51, that could rescue altered neuronal network activity. With RSRT support, the team will now screen a larger library of drugs and in parallel test NCH-51 in mice models of the duplication syndrome. Read more about the project here.

Rett Syndrome – Award of $209,000

We know that the levels of MeCP2 protein must be tightly controlled in the brain. Too little leads to Rett Syndrome, whereas too much leads to the duplication syndrome. How exactly the correct levels of MeCP2 maintain the proper function of neuronal networks is an important and fundamental question. With RSRT support, Dr. Muotri and his team will genetically engineer human pluripotent stem cells to control MeCP2 levels. This work has the potential to reveal novel therapeutic opportunities for Rett Syndrome and will also be informative for future gene therapy/protein replacement, where the amount of MeCP2 to be delivered to the brain is critical. Read more about the project here.

As always at RSRT, our priority is changing the lives of those struggling with Rett and MECP2 Duplication. We are confident that Dr. Muotri’s work will provide information and data that are critical to numerous approaches we are taking to accomplish this. None of this important research would be possible without all who support RSRT. Thank you.