Development of an In-Vitro Cell System For Discovering and Evaluating the Effects of Therapeutic Candidates on Neurons Produced Using Rett Patient iPS Cells

Q-State BioSciences

$828,141 AWARDED

Specific mutations in a single gene, MECP2, can be identified in the vast majority of individuals with Rett Syndrome. However, the Rett mutation is just a part of the person’s genome and each person is unique. Precision medicine is a new and innovative approach to treatment that takes into account individual differences in people’s genes, environments, and lifestyles. Rather than focusing on developing treatments for the “average person” with Rett Syndrome, successful implementation of precision medicine will help optimize treatment for each individual. This grant leverages the significant progress already achieved in our collaboration with Q-State BioSciences to further advance our goal of implementing precision medicine in the treatment of Rett Syndrome.

To date, the fundamental obstacle 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. Similar to most diseases, it is often difficult to predict response to treatment and sequential trials of therapeutics are often required to identify the optimal regimen for each person. Our goal is to make this trial and error approach obsolete.

RSRT is collaborating with Q-State Biosciences to enable precision medicine for individuals with Rett Syndrome. The company has developed methods that use cells from individuals with mutations in MECP2, to study disease, explore possible treatments, and, hopefully predict an individual’s response to specific therapeutics. In essence, a small snippet of a patient’s skin or blood is converted into stem cells (also called induced pluripotent stem cells). These cells carry the patient’s disease causing mutation along with their entire genome. Q-State then converts these stem cells into neurons, and studies these “brain in a dish” cultures.

In the present study, we are optimizing the processes for generating the “brain in a dish” cultures and further characterizing the changes that result from the Rett mutations. 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 our curative programs such as gene therapy, RNA editing, MECP2 reactivation and RNA trans-splicing to downstream targeted drugs such as ketamine. 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.