•Independent peer-reviewed study confirms high potential for OligoPhoreTM delivery platform in RNA-based treatments for osteoarthritis •Knock down of JMJD3 gene remarkably mitigated severity of joint degeneration in animal model
HAMILTON, BERMUDA , July 28, 2022 (GLOBE NEWSWIRE) —
Altamira Therapeutics (“Altamira” or the “Company”) (NASDAQ:CYTO), a company dedicated to developing therapeutics that address important unmet medical needs, today announced the publication of a peer-reviewed article in the scientific journal International Journal of Oral Science titled, “Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1” that covers an independently funded study evaluating novel treatment approaches for osteoarthritis (OA) conducted by a Shanghai-based research group.
The study used different approaches to downregulate the Jumonji domain-containing protein D3 (JMJD3) gene to assess whether this strategy would be beneficial for the treatment of OA. Nanoparticles comprising a siRNA targeting the JMJD3 gene, and Altamira’s peptide-based OligoPhore delivery platform (also known as “p5RHH”), were used to locally downregulate the expression of JMJD3 in a mouse model of OA. The study authors observed that, “the severity of joint degeneration was remarkably mitigated” thanks to administration of the nanoparticles and highlighted their “advantage of specifically targeting inflammation in the joint without off-target toxicities.” They propose JMJD3 inhibition – based on the OligoPhore platform – as an “innovative epigenetic therapy approach for joint diseases.”
In their study, the authors pursued an epigenetic-based therapeutic approach (i.e. targeting gene regulation) to mitigate cartilage inflammation and damage in a murine model of osteoarthritis. OligoPhore was used to formulate siRNA polyplexes that inhibited chondrocyte production of a histone demethylase, JMJD3, in response to joint damage. JMJD3 is upregulated in joint injury and drives other inflammatory pathways to elicit further damage and chondrocyte programmed cell death. Injection of 2 weekly doses of OligoPhore-siRNA into the affected joint over 8 weeks significantly attenuated inflammation and preserved cartilage viability and integrity.
“The study’s results confirm prior findings reporting the benefit of RNA therapeutics based on our nanoparticle delivery platform in models in rheumatoid arthritis and, now, osteoarthritis,” commented Samuel Wickline, MD, Altamira Therapeutics’ Chief Scientific Officer.” One of the key features of OligoPhore is the targeted delivery to inflamed tissues, making it particularly well suited for the treatment of arthritis with oligonucleotides, both in terms of efficacy and safety.
“Osteoarthritis can have a significantly detrimental impact on the well-being and quality of life of patients, often over many years or even decades, yet there is still no disease-modifying treatment available,” Dr. Wickline added. “While our AM-411 program is targeting rheumatoid arthritis, we envision extending its potential use to osteoarthritis as well.”
Earlier this week, the Company announced the initiation of AM-411, a development program based on its proprietary OligoPhore delivery platform and siRNA targeting NF-κB, for a novel generation of rheumatoid arthritis (RA) therapeutics.
Osteoarthritis to become one of the most prevalent diseases in the coming decades
Osteoarthritis is a degenerative joint disease that can affect the many tissues of the joint.1 It can degrade cartilage, change bone shape and cause inflammation, resulting in pain, stiffness and loss of mobility. OA can affect any joint, but typically affects hands, knees, hips, lower back and neck. Its signs and symptoms typically show up more often in individuals over age 50, but OA can affect much younger people, too, especially those who have had a prior joint injury. There is no cure for OA, but there are ways to manage OA to minimize pain, continue physical activities, maintain a good quality of life and remain mobile.
OA is by far the most common form of arthritis, affecting more than 32.5 million adults in the United States, according to the Centers for Disease Control and Prevention. The global prevalence of OA is increasing and the burden of the disease will rise.2 The medical cost of osteoarthritis in various high-income countries has been estimated to account for between 1% and 2.5% of the gross domestic product of these countries, with hip and knee joint replacements representing the major proportion of these health-care costs.
About International Journal of Oral Science
The International Journal of Oral Science seeks to publish all aspects of oral science and interdisciplinary fields, including basic, applied and clinical research. The Journal publishes peer-reviewed articles that describe new research results and review articles that provide succinct summaries of an area in oral science. The International Journal of Oral Science is published by Springer Nature. For more information, visit: https://www.nature.com/ijos/aims
OligoPhore is a versatile platform for safe and effective delivery of oligonucleotides such as siRNA (small interfering ribonucleic acid) into target cells. It is based on a proprietary 21-amino acid peptide that can engage any type of RNA in rapid self-assembly into a polyplex. The polyplex has a size, charge, and other physical features that allow it to escape hepatic clearance and thus to reach other target tissues than the liver. OligoPhore protects the RNA payload from degradation in the circulation and allows for rapid cellular uptake, while enabling pH-dependent nucleotide endosomal escape and cytoplasmic delivery. Effective delivery and positive treatment outcomes have been demonstrated in more than 10 murine models of disease for targets in the NF-κB family, various members of the ETS transcription factor family, and targets in the JNK and TAM pathways.
About Altamira Therapeutics
Altamira Therapeutics (NASDAQ:CYTO) is dedicated to developing therapeutics that address important unmet medical needs. The Company is currently active in three areas: the development of RNA therapeutics for extrahepatic therapeutic targets (OligoPhore™ / SemaPhore™ platforms; preclinical), nasal sprays for protection against airborne allergens and, where approved, viruses (Bentrio™; commercial) or for the treatment of vertigo (AM-125; Phase 2), and the development of therapeutics for intratympanic treatment of tinnitus or hearing loss (Keyzilen® and Sonsuvi®; Phase 3). Founded in 2003, it is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com/
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2 Hunter DJ & Bierma-Zeinstra S (2019), Osteoarthritis, Lancet 393:1745-59.