Oral presentation of new preclinical data at American Society of Gene and Cell Therapy (ASGCT) 25th Annual Meeting
SAN DIEGO, May 19, 2022 – Locanabio, Inc., a genetic medicines company developing RNA-targeted therapeutics for patients with severe neuromuscular and neurodegenerative diseases, today announced the presentation of new preclinical data on its proprietary CORRECTx™ platform for the potential treatment of amyotrophic lateral sclerosis (ALS). The data, generated in vitro and in a mouse model of ALS, demonstrate that a single administration of the CORRECTx RNA-targeting gene therapy reduced toxic RNA transcripts from hexanucleotide (G4C2) repeat expansions in the chromosome 9 open reading frame 72 (C9ORF72) gene that are known to be associated with ALS in humans.
“These new data demonstrate the potential advantages of our CORRECTx technology, which can be designed to selectively target both disease-causing sense and antisense RNA transcripts in a single construct while sparing expression of the wild-type C9ORF72 allele which may be important for cellular function,” said John Leonard, Ph.D., chief scientific officer of Locanabio. “These studies support further development of our CRISPR-Cas13d multi-guide RNA-targeting system as a potential therapeutic approach for ALS and other neurologic disorders associated with this locus.”
A G4C2 hexanucleotide repeat expansion in the C9ORF72 gene is the most common genetic cause of familial ALS and frontotemporal dementia (FTD). Transcription at the C9ORF72 repeat locus produces both sense (GGGGCC or G4C2) and antisense (CCCCGG or C4G2) RNA transcripts that accumulate as foci in the nucleus as well as dipeptide repeat protein products that aggregate and cause neuronal toxicity in the brain and spinal cord. In the studies presented at ASGCT, Locanabio used its CORRECTx platform comprising a CRISPR-Cas13d system with two guide RNAs designed to target both disease-causing sense and antisense RNA repeats packaged into a single AAV9 vector for delivery. Significant reduction of toxic RNA products was observed in isolated cells. Following one-time administration of the RNA-targeting CRISPR-Cas13d system in the C9ORF72 ALS model, a decrease in toxic G4C2 transcripts was observed without reduction in total C9ORF72 RNA levels. Additional data demonstrate that the expression of the CRISPR-Cas13d multi-guide system was well tolerated post-administration throughout the 10-week study.
“The versatility of our selective CORRECTx RNA-targeting approach provides Locanabio with several advantages as we advance development candidates from our novel class of genetic medicines to other disease targets,” said James Burns, Ph.D., chief executive officer of Locanabio. “We are pleased with the progress of our ALS program and are very encouraged by these data presented today, which supports our plans to leverage the multi-targeting and mutation specific capabilities of the CORRECTx platform to expand our pipeline and treat other serious diseases with limited or no treatment options.”
The data are being presented today at 10:45 a.m. ET at the ASGCT 25th Annual Meeting, taking place May 16-19, 2022 in Washington, D.C. The oral presentation, titled “AAV9 mediated delivery of RNA targeting systems eliminate hexanucleotide repeat expansions in C9ORF72 ALS/FTD models,” is available on the Events & Presentations section of the Locanabio website at https://locanabio.com/wp-content/uploads/2022/05/2022-ASGCT.pdf.
Amyotrophic lateral sclerosis (ALS) is a genetic motor neuron disorder caused by a mutation in the C9ORF72 gene, resulting in hexanucleotide (G4C2 and C4G2) repeat expansions. These toxic RNA repeats lead to disease symptoms including progressive muscle weakness, muscle cramps and twitching, difficulty walking, swallowing and breathing, and cognitive and behavioral changes. ALS symptoms often start in the hands, feet, limbs, or spine and then spread to other parts of the body. Familial ALS, a hereditary form of the disease, is estimated to account for about 10 percent of all ALS cases while sporadic ALS accounts for about 90 percent. C9ORF72 hexanucleotide repeat expansions are estimated to account for about 40 percent of familial ALS cases and about 10 percent of sporadic ALS cases.
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. Locanabio’s 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. CORRECTx is 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. The company is currently focused on advancing programs in neuromuscular and neurodegenerative diseases. For more information, visit www.locanabio.com.
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