Secarna Pharmaceuticals’ Antisense Oligonucleotide Therapy Shows Promise for Treating Inflammatory Diseases

Secarna Pharmaceuticals Announces Promising Preclinical Results in the Treatment of Inflammatory Diseases

ASO Therapy Shows Potential in Suppressing IL-1β Expression

Secarna Pharmaceuticals GmbH & Co. has recently revealed remarkable preclinical data demonstrating the efficacy of antisense oligonucleotide (ASO) therapy in the treatment of inflammatory diseases. This breakthrough was published in the esteemed peer-reviewed journal, “The Journal of Immunology”. The study titled, “Antisense Oligonucleotide Therapy to Suppress IL-1β Expression and Extend Life in Nlrp3 Mutant Mice”, was conducted by renowned scholars Professor Ariel Feldstein and Professor Hal Hoffman, along with collaboration from the University of California, San Diego.

Secarna leveraged its cutting-edge Oligofyer™ bioinformatics system to design a specific ASO, based on the LNAplus™ platform, that inhibits the expression of NLR family pyrin domain containing 3 (NLR3). NLR3 is a crucial component of the inflammatory pathway. Activation of the inflammasome results in the secretion of inflammatory cytokines, such as IL-1β. If this pathway becomes hyperactivated, it can lead to various inflammatory diseases, including arthritis, inflammatory bowel disease, kidney disease, non-alcoholic steatohepatitis, asthma, and central nervous system disorders like Parkinson’s and Alzheimer’s disease. Secarna’s study demonstrates that ASO treatment targeting NLRP3 and IL-1β can potentially serve as a therapeutic approach for conditions like CAPS and other NLRP3-mediated diseases.

CAPS refers to a range of autoinflammatory diseases triggered by the activation of NLRP3 gene mutations. Existing therapies, focusing on inhibiting the IL-1β pathway, have shown improvement in clinical symptoms for some patients. However, there is a significant population of non-responders, emphasizing the need for more effective treatments.

“Our preclinical results reveal that NLRP3-specific ASOs have the ability to successfully target genes involved in CAPS and suppress the overactivity of the inflammatory cascade,” affirmed Dr. Frank Jaschinski, Chief Scientific Officer at Secarna Pharmaceuticals. “We are particularly delighted to observe significant therapeutic effects in related organs, indicating that these ASOs can potentially address various diseases associated with an overactive NLRP3 inflammatory pathway, such as inflammatory bowel disease, kidney disease, and central nervous system disorders. Furthermore, we anticipate exploring new possibilities of ASO therapy in areas where no approved treatment currently exists.”

Simultaneously, the University of California, San Diego conducted in vitro and in vivo testing on the potential of NLRP3-ASO therapy for treating CAPS. Their research confirmed the robust suppression of gene expression in cultured cells. Additionally, they observed a reduction in the secretion of IL-1β, an inflammatory cytokine, in immune cells derived from an in vivo CAPS model. Further testing of NLRP3-ASO therapy on an in vivo NOMID disease model demonstrated that systemic ASO treatment significantly improved life expectancy, body weight, and overall systemic inflammation, while also reducing the severity of skin lesions.

[팜뉴스=이권구 기자] Secarna Pharmaceuticals GmbH & Co., a biopharmaceutical company focuses on the discovery and development of next-generation antisense oligonucleotide (ASO) therapies to treat targets that were difficult or impossible to treat through the current LNAplus™ platform. KG published preclinical data showing the efficacy of ASO in the treatment of inflammatory diseases in the peer-reviewed journal ‘The Journal of Immunology’.

The title is ‘Antisense oligonucleotide therapy to suppress IL-1β expression and extend life in Nlrp3 mutant mice’, Professor Ariel Feldstein and Professor Hal Hoffman, world-renowned scholars in NLRP3 and CAPS mediated inflammation, and Secarna, University of California, San Diego is a collaborative study.

Secarna leveraged its Oligofyer™ bioinformatics system to design an LNAplus™ ASO that specifically inhibits the expression of NLR family pyrin domain containing 3 (NLR3), a key component of the inflammatory pathway.

According to the company, when the inflammasome is activated, inflammatory cytokines such as IL-1β are secreted, and hyperactivation of this pathway can lead to arthritis, inflammatory bowel disease, acute and chronic kidney disease, steatohepatitis non-alcohol, asthma, Parkinson’s disease and It plays an important pathological role in many inflammatory diseases, including diseases of the central nervous system such as Alzheimer’s disease. This study shows that NLRP3-specific ASO treatment down-regulates NLRP3 expression and IL-1β secretion in a CAPS disease model, suggesting that ASO therapy can be used as a potential therapy for CAPS and other NLRP3-mediated diseases, he explained the company that made it.

CAPS is a spectrum of autoinflammatory diseases that occur when NLRP3 gene mutations are activated. Current therapies are designed to inhibit the IL-1β pathway and have been shown to improve clinical symptoms in patients, but trials are not recommended clinical for non-responders. Better therapies are needed because the needs are not being met.

“With these preclinical results, we show that NLRP3-specific ASOs can effectively target genes of interest across the CAPS spectrum and block the overactivity of the inflammatory cascade,” said Dr. Frank Jaschinski, Chief Scientific Officer, Secarna Pharmaceuticals. In the model, we are delighted to confirm that multiple tests of related organs show clear therapeutic effects, and these data suggest that this ASO is caused by an overactive NLRP3 inflammatory pathway, including inflammatory bowel disease , acute and chronic kidney disease, and central nervous system disease. “It opens up the possibility of treating other diseases that are currently being treated. We look forward to developing ASOs that target inflammation in an area where there is no approved ASO therapy to date.”

Meanwhile, according to the company, a research team at the University of California, San Diego campus tested the possibility of NLRP3-ASO for CAPS treatment in in vitro and in vivo models and proved that NLRP3-ASO strongly suppresses gene expression in culture cells.

In addition, secretion of the inflammatory cytokine IL-1β was shown to be reduced in cultured immune cells derived from the all-type in vivo CAPS model. NLRP3-ASO was tested in an in vivo NOMID disease model (the most severe form of CAPS) and treatment with systemic ASO was found to significantly increase life expectancy, increase body weight, and reduce overall systemic inflammation with less severity of skin lesions .

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