– New data show allele-specific reduction of CUG repeats and corrected splicing and myotonia in HSALR mice across multiple leads
– Company is advancing multiple DM1 leads into non-human primate studies in 2022
SAN DIEGO, November 18, 2021 – 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. Using its CORRECTxTM 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.
“We are pleased with the continued progress of our DM1 program. 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. “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. 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.”
The data were presented at the Society for Muscle Biology’s Frontiers in Myogenesis Conference 2021, taking place November 15-19 in Costa Rica. 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 https://locanabio.com/wp-content/uploads/2021/11/Muscle_Society.pdf.
Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disorder affecting skeletal muscle, cardiac muscle, the gastrointestinal tract, and the central nervous system. DM1 is caused by a mutation in the myotonic dystrophy protein kinase (DMPK) gene. This mutation leads to a repeat expansion of the CTG trinucleotide. The expanded CTG is transcribed into toxic CUG repeats in the DMPK RNA. 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 incidence of myotonic dystrophy is estimated at one in 8,000 individuals worldwide or approximately 40,000 people in the United States.
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. Our proprietary platform, CORRECTx™, uses gene therapy to deliver RNA-binding protein systems that can be engineered to selectively manipulate disease-causing RNA by multiple mechanisms. Our systems are designed to provide a durable therapy with a single administration without altering a cell’s DNA. Locanabio’s CORRECTx platform has applications across a range of tissues and diseases and we are currently advancing programs in neurodegenerative, neuromuscular and retinal diseases. For more information, visit www.locanabio.com.
Berry & Company