Stoke Therapeutics Presents New Data That Demonstrate Tango Antisense Oligonucleotides (ASOs) Increase OPA1 Protein Production and Improve Mitochondrial Function in Cells Derived From Patients With Autosomal Dominant Optic Atrophy (ADOA)
– Results presented at ARVO annual meeting confirm earlier preclinical findings and support the Company’s work to discover and develop the first potential disease modifying approach for the treatment of ADOA –
– ADOA is the most common inherited optic nerve disorder –
“These findings are important because they offer the first evidence from patient cells that our TANGO approach can address the underlying cause of ADOA by upregulating OPA1 protein production and increasing mitochondrial function,” said
ADOA affects approximately one in 30,000 people globally with a higher incidence in
“By demonstrating an improvement in the mitochondrial function of patient cells across different OPA1 mutations, the data suggest that ASO mediated increase in OPA1 could be sufficient to slow or reduce disease progression in a mutation-independent manner,” said
The data presented today provide in-vitro proof-of-concept for TANGO ASOs in ADOA patient fibroblasts. Highlights from today’s presentation include new data that demonstrate ADOA patient fibroblast cell lines treated with TANGO ASOs exhibit:
- Reduced non-productive exon inclusion and increased total OPA1 mRNA expression in three patient fibroblast cell lines with different mutations;
- Increased expression of multiple OPA1 protein isoforms by ~35% to 47%; and
- A dose-dependent improvement in mitochondrial bioenergetics.
Details of today’s presentation are as follows:
Presentation Title: Antisense oligonucleotide mediated increase in OPA1 improves mitochondrial function in fibroblasts derived from patients with autosomal dominant optic atrophy (ADOA)
Session Date & Time:
Session Title: Gene therapy in ocular diseases
The presentation at ARVO is now available online on the Events and Presentations section of Stoke’s website at https://investor.stoketherapeutics.com/.
About Autosomal Dominant Optic Atrophy (ADOA)
Autosomal dominant optic atrophy (ADOA) is the most common inherited optic nerve disorder. It is a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Symptoms typically begin between the ages of 4 and 6 years old, affecting males and females equally. The severity of the condition by adolescence reflects the overall level of visual function to be expected throughout most of the individual’s adult life. Roughly half of people with ADOA fail driving standards and up to 46% are registered as legally blind. ADOA is considered a haploinsufficiency disease, as most people living with ADOA have genetic mutations in the OPA1 gene that result in only half the necessary OPA1 protein being produced. More than 400 OPA1 mutations have been reported in people diagnosed with ADOA. Currently there is no approved treatment for people living with ADOA. ADOA affects approximately one in 30,000 people globally with a higher incidence in
TANGO (Targeted Augmentation of Nuclear Gene Output) is Stoke’s proprietary research platform. Stoke’s initial application for this technology are diseases in which one copy of a gene functions normally and the other is mutated, also called haploinsufficiencies. In these cases, the mutated gene does not produce its share of protein, so the body does not function normally. Using the TANGO approach and a deep understanding of RNA science, Stoke researchers design antisense oligonucleotides (ASOs) that bind to pre-mRNA and help the target genes produce more protein. TANGO aims to restore missing proteins by increasing – or stoking – protein output from healthy genes, thus compensating for the non-functioning copy of the gene.
Cautionary Note Regarding Forward-Looking Statements
This press release contains “forward-looking” statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: preclinical data and study results regarding OPA1; our ability to develop TANGO ASOs to treat the underlying causes of ADOA and increase mitochondrial function; our ability to advance OPA1 as our next preclinical target; and the ability of TANGO to design medicines to increase protein production and the expected benefits thereof. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain regulatory approval for and commercialize any potential clinical candidate for OPA1; the timing and results of preclinical studies and clinical trials; the risk that positive results in a preclinical trial may not be replicated in subsequent trials or success in early stage preclinical trials may not be predictive of results in later stage trials; failure to protect and enforce our intellectual property, and other proprietary rights; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with current and potential future healthcare reforms; and the other risks and uncertainties that are described in the Risk Factors section of our most recent annual or quarterly report and in other reports we have filed with the
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