Team Titin is a nonprofit organization with the mission of serving those living with, caring for, or researching titin (TTN) related muscle and heart disorders. Team Titin is excited to announce our first research grant funding award to Dr. Isabelle Richard, PhD (Principal Investigator, Head of the Progressive Muscular Dystrophies Laboratory at Genethon), in collaboration with Dr Sonia Albini and Dr Edoardo Malfatti Team Titin will fund $50,000 over two years to support the project, “Generation and characterization of skeletal muscle organoids from TTN patients’ iPSC for therapeutic screening.”
Disease-causing changes in the TTN (titin) gene can cause a spectrum of muscle and/or heart disorders known as “titinopathy”. This giant protein plays a role in the stability and organization of the muscle cell. It also works as a molecular spring for the passive elasticity of muscle.
It is unpredictable how the titin protein will be affected by a given genetic change and how this might impact a patient’s symptoms. Future therapeutic approaches also might be unpredictable. Organoids, however, can be used to test drug treatments. Organoids are three-dimensional, muscle-tissue cultures derived from patients’ blood cells and are then programmed and differentiated into muscle. In this study, Dr. Richard and her team will examine the mutated titin proteins and their function and then use the organoids to test treatments. In summary, artificial muscles with the abnormal titin protein will be created, tested with various drugs and analyzed for its impact on function.
This project will be managed at Genethon, a not-for-profit organization, a pioneer and leader in gene therapy with the mission to develop treatments that change the lives of patients suffering from rare genetic diseases and to eradicate these pathologies.
Dr. Isabelle Richard, PhD, the principle Investigator, is a research Director at the CNRS. She is heading the Muscular Dystrophies team within the INSERM U951 in Genethon, Evry, France. Dr. Richard is an expert in the molecular genetics of neuromuscular diseases. She has published more than 185 papers on genetics of muscular dystrophy, identification of pathophysiological mechanisms of the diseases, identification of biomarkers, development of animal models and proof-of principle of therapeutic strategies especially gene therapy. She is now involved in translating different gene therapies for muscle diseases into the clinics and has recently co-founded the company Atamyo Therapeutics with this objective in mind.
Dr. Sonia Albini, PhD, is a senior scientist in the Muscular Dystrophies team at Genethon, within the INSERM U951. Her research focuses on translational research for progressive muscular dystrophies. Her expertise covers Duchenne Muscular Dystrophy, Regenerative Medicine, Bioengineering, Stem Cells and Disease modeling. She has published 21 peer-reviewed papers in the field, and she is now involved in the establishment of in vitro preclinical models of disease, using pluripotent stem cells of patients, suitable as screening platform for gene therapy and pharmacological approaches. She will supervise the work of generating muscle organoids carrying TTN mutation from patient’ stem cells and the identification or development of assays to detect the pathogenic hallmarks of specific TTN mutations.
Edoardo Malfatti, MD, PhD: Prof. Malfatti is a Neurologist and Myopathologist at Paris Est University with a deep expertise in clinical, muscle morphologic, and genetic characterization of inherited myopathies. In 2015 Prof. Malfatti was awarded as Young Myologist of the year by the President of the World Muscle Society. He has contributed to the fine clinical and myopathologic characterization of many myopathies including Titinopathies. Dr Malfatti will provide patients’ cells and will be involved in scientific discussion and interpretation of the results.
Team Titin is deeply appreciative of all the contributions that made this funding possible and we are excited about the potential future results of this grant project.
