We are committed to raising funds to support research for treatments and a cure for CTNNB1 Syndrome. While the medical journeys that our children undergo are often full of the unknown, rare disease organizations and medical researchers around the world have helped chart the course that we need to take to get to our end goal.
Our Research Priorities
Boston Children’s Hospital’s Wendy Chung, MD, PhD, serves on our Scientific Advisory Board. In the video below, she outlines the steps that we need to take to find a cure for CTNNB1 Syndrome. This process also aligns with our research priorities, which include:
- Developing a comprehensive Patient Registry and Natural History Study that documents our children’s mutations, developmental milestones and clinical data
- Growing a colony of mice (also known as a mouse model) with a whole body deletion of one copy of the gene to understand how different gene mutations lead to differences in molecular and functional changes
- Defining the molecular and functional changes caused by the full body deletion of one CTNNB1 allele
- Developing human derived neurons to asses the molecular changes and effectiveness of treatment approaches as identified in mouse model studies
- Partnering with biotech and pharmaceutical companies to advance the development of treatments
Current Progress
In our first grant, Michele Jacob, PhD, and her team at Tufts University created a mouse model with a full body deletion of one CTNNB1 allele. Since then, she and her team have bred a colony of CTNNB1 syndrome mice to be used in treatment experiments.
A great deal of time was also spent on defining the molecular and functional changes caused by this full body deletion. This included tests for learning and motor skills as well as defining the molecular and functional underpinnings in three tissue types: brain, spinal cord, and skeletal muscle.
The studies show reductions in beta-catenin levels, learning and muscle strength, confirming the value of this new mice model for in vivo tests of drug treatments to correct these changes. Further, ongoing experiments continue to look at age dependent changes both progressive and compensatory by assessing selected stages from infancy to adulthood.
Our second grant to Dr. Jacob funds a collaboration with two molecular chemists for the testing of high selectivity drugs to target beta-catenin and the Wnt signaling pathway to restore function. The goal is to correct reduced beta-catenin levels to more normal baseline levels to increase cognitive and motor function in our mice.
The drug treatments started in March 2021 and will be continuously ongoing to complete the plan to test multiple high selectivity drugs at multiple stages of administration. The plan includes a battery of tests to assess improvements in learning, motor skills, as well as molecular and functional changes. Additionally, tests will be conducted to verify the absence of adverse side effects.
Dr. Jacob is now focused on developing human neuron and skeletal muscle cells with the deletion of one CTNNB1 allele. A collaboration is already underway with two experts to generate human neurons and skeletal muscles differentiated from induced pluripotent stem cells. These cells will be used to test whether the drug treatments that provide effective remedies in our mice model are also effective in human cell types relevant to CTNNB1 syndrome.
Once completed, our preclinical models will provide the essential proof of concept that the drug treatments that we are exploring are both safe and effective. Data from both in vivo mouse and in vitro human cell models will provide the essential foundation needed to compete for external grants and to garner interest from venture capital investors and pharmaceutical companies.
Moving forward, we will continue to fund research for molecular development and drug intervention to improve the quality of life for our current patient population. At the same time, we will also be conducting the necessary groundwork research to prepare us for gene replacement and other cutting edge approaches.
Meet Michele H. Jacob, Ph.D.
Michele Jacob, Ph.D. is a Professor in the Department of Neuroscience at Tufts University School of Medicine in Boston, Massachusetts. She received her B.S. in biology from City College of New York, her Ph.D. from Yale University in cell biology, and she completed postdoctoral training in neurobiology at Columbia University and at The University of California, San Diego. She then headed her own laboratory in the neurobiology group at the Worcester Foundation for Biomedical Research, prior to moving to Tufts University. Dr. Jacob, along with her lab’s postdoctoral scholar, Jon Alexander, is dedicated to working with CCC to advance the design of new and effective treatment strategies.