Injury-mediated regulation of these processes in healthy cells, their downstream effectors and the role of mitochondrial interactions with other organelles in controlling this repair mechanism are some of the other open questions. We study how mutations that alter mitochondrial calcium uptake, ROS production or fission, compromise cell repair and lead to muscle diseases. Despite being organized in a cell-wide network, mitochondria can act locally by controlled mitochondrial fission at the site of injury. This ROS locally activates the reorganization of actin cytoskeleton to enable closure of the cellular wound. We find that calcium that enters the injured cell is taken up by mitochondria in a regulated manner which allows controlled production of reactive oxygen species (ROS). Research focus areas include muscular dystrophy, membrane trafficking, genetic diseases of muscle such as Duchenne muscular dystrophy, heart failure, steroid signaling/gene expression and microRNA regulation.Ī serendipitous discovery that mitochondrial proteins accumulate at the injured cell membrane and mitochondria in muscle fiber can accumulate at the site of injury, led us to studies that have uncovered the requirement of mitochondria in repairing cell membrane injury.
The Center for Genetic Medicine Muscle Group focuses on understanding the cell biology of muscle and degenerative diseases.
Locanabio is a leader in developing a new class of genetic medicines that has the potential to significantly improve the lives of patients with devastating genetic diseases by correcting the message of disease-causing RNA. The incidence of myotonic dystrophy is estimated at one in 8,000 individuals worldwide or approximately 40,000 people in the United States. These toxic RNA repeats lead to disease symptoms including progressive muscle wasting, weakness and myotonia (delayed relaxation of skeletal muscle), a hallmark of DM1. The expanded CTG is transcribed into toxic CUG repeats in the DMPK RNA. This mutation leads to a repeat expansion of the CTG trinucleotide. DM1 is caused by a mutation in the myotonic dystrophy protein kinase (DMPK) gene. Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disorder affecting skeletal muscle, cardiac muscle, the gastrointestinal tract, and the central nervous system. The poster presentation, titled "AAV9 Mediated Delivery of RNA Targeting Systems Corrects Molecular and Functional Defects in Myotonic Dystrophy Type 1," is available on the Events & Presentations section of the company's website at. The data were presented at the Society for Muscle Biology's Frontiers in Myogenesis Conference 2021, taking place November 15-19 in Costa Rica. We are very encouraged by these data and believe they support the application of our CORRECTx platform to treat DM1 as well as additional repeat expansion disorders." "Additionally, the data demonstrate our ability to preferentially target the toxic, mutant allele and preserve DMPK RNA generated from the wild-type allele, which is one of several distinguishing features of our CORRECTx platform. These data demonstrate a robust reduction of toxic RNA foci, a hallmark of this repeat expansion disorder, in the nucleus as well as the correction of splicing and a significant reduction of myotonia with Cas13d and PUF constructs via different mechanisms of action," said John Leonard, Ph.D., chief scientific officer at Locanabio. "We are pleased with the continued progress of our DM1 program. Using its CORRECTx ™ platform, Locanabio scientists demonstrated a dose-dependent reduction in toxic CUG foci in both DM1 patient muscle cells and in a preclinical mouse model of DM1 that led to a correction in alternative RNA splicing and a statistically significant reduction in myotonia, or muscle weakness. 18, 2021 /PRNewswire/ - Locanabio, Inc., a genetic medicines company developing therapeutics for patients with severe neuromuscular, neurodegenerative and retinal diseases, today announced the presentation of new preclinical data from its myotonic dystrophy type 1 (DM1) program.