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Precision Medicine

Mutations in a single gene, MECP2, can be identified in the vast majority of individuals with Rett Syndrome, yet each person is unique. As in any disease, treatments such as seizure or anxiety medications can be very successful for some individuals but not for others, even for those with the exact same genetic mutation. As a result, sequential trials of therapeutics are often required to identify the optimal regimen for each person. It is our hope that this trial and error approach will become obsolete with the emergence of precision medicine, an innovative approach to treatment that takes into account individual differences in people’s genes, environments, and lifestyles.

One of the fundamental obstacles in implementing precision medicine for individuals with Rett Syndrome has been the lack of an efficient method for evaluating how an individual’s ‘genetic background’ interacts with the mutation in MECP2 to modify symptoms and disability. That is, the Rett mutation is just a part of the person's genome. The onset, severity, and response to treatment will likely vary based not only on the mutation in MECP2, but also by the differences in the background genetic makeup of each individual with Rett Syndrome.

RSRT is collaborating with Q-State Biosciences to overcome this obstacle and enable precision medicine for individuals with Rett Syndrome. Q-State Biosciences is an integrated drug discovery company with a mission to develop precision diagnostics and treatments for disorders of the nervous and cardiac systems. The company has developed methods to use a patient's own cells to study disease, explore possible treatments, and, potentially even predict an individual's response to specific therapeutics. In essence, Q-State has developed technical methods to convert a small snippet of a patient's skin or blood into stem cells. These stem cells (also called induced pluripotent stem cells) carry the patient's disease causing mutation along with the individual's entire genome. Q-State then converts these stem cells into neurons, which mature in a dish and begin to connect with other neurons and communicate much as happens in the person's own brain and nervous system. Q-State also has developed methods to study the behavior of cells and assess the effects of therapeutics in these ‘brain in a dish’ cultures. Therapeutics such as drugs will be tested but also biological approaches such as gene therapy and protein replacement. Q-State's methods have been successfully applied to a number of neurodegenerative, neurodevelopmental, and neuropsychiatric diseases.

Q-State and the Rett Syndrome Research Trust are now working together to apply these methods to study patients with Rett Syndrome. In the present study, we are characterizing the changes that result from the Rett mutation. We will then identify drugs, genes, and other therapeutics that correct these changes in cell lines generated from individuals with a range of different MECP2 mutations. The next step will be to confirm that the best therapeutics identified in these ‘brain in a dish’ assays actually predict the best therapeutics for that same individual. If so, the Q-State system could ultimately be used for a precision medicine approach to select treatments that will work best for each individual with Rett Syndrome.

We’re excited about this because it has implications for all of our programs - from gene therapy that offers a potential cure, to drugs such as ketamine and statins that address multiple symptoms. It’s telling of how far we have come, and how far we expect to go, that we are starting to look ahead at how to maximize the impact of each of our approaches on individuals.