State Grant Supports Osteoarthritis Gene Therapy Trial

(AKha, Wikimedia Commons)

24 Feb. 2023. A California state agency is funding a clinical trial of an experimental gene therapy for reducing inflammation in knee joints of people with osteoarthritis. Genascence Corp. in Palo Alto, California is receiving an $11.6 million award over four years from the California Institute for Regenerative Medicine or CIRM, a state health research agency.

Genascence Corp. is a six year-old biotechnology enterprise that seeks to extend use of gene therapies from inherited disorders to address more common conditions faced by individuals. The company licenses research by its scientific founders at the Mayo Clinic and University of Florida that study molecular and cell biology, as well as genetics and biology of aging. Genascence says its lead product, code-named GNSC-001, is designed to block chemical signals promoting inflammation and joint pain from osteoarthritis in the knee.

Osteoarthritis is a common condition associated with aging, where years of wear and tear breaks down protective cartilage in the joints. Symptoms often develop slowly and worsen over times that include pain, stiffness, tenderness, loss of flexibility, swelling, and in some cases bone spurs that develop around the joints. Centers for Disease Control and Prevention says about one in four adults in the U.S. — 24 percent or 58.5 million people — are diagnosed with arthritis of all kinds, with women more likely than men to have the condition, as well as people who are overweight or obese.

Most treatments today for osteoarthritis aim to relieve the pain symptoms and manage the condition. GNSC-001, says Genascence, seeks to block inflammatory signals in knee joints from the protein Interleukin 1 or IL-1. GNSC-001 is injected one time into the joint to provide a healthy gene that codes for another protein, IL-1 receptor antagonist, to operate in synovial membrane cells. The synovium is a connective soft tissue that produces synovial fluid lubricating the joints.

Address causes of the inflammation, not just symptoms

Genascence says IL-1 receptor antagonist proteins are produced by the injected gene, delivered with a benign adeno-associated virus in the synovium, where they bind to other receptor proteins generated by IL-1. Those other IL-1 receptors would normally activate inflammatory signals in the joints, causing the pain, stiffness, and swelling of osteoarthritis. But, says Genascence, the IL-1 receptor antagonist proteins block the actions of other IL-1 receptors, preventing further inflammation.

The company notes GNSC-001 is designed to offer one-time sustained blocking of IL-1, thus addressing more of the causes of inflammation from osteoarthritis. “Current treatment options are short-term,” says Genascence CEO Thomas Chalberg in a company statement released through Cision, “and while they can provide temporary relief of symptoms, they do not slow down or reverse disease progression.”

The company conducted an early-stage clinical trial of GNSC-001, with results reported in May 2022 at a meeting of the American Society of Gene and Cell Therapy. The trial enrolled nine individuals with moderate osteoarthritis in their knees, looking mainly for adverse effects from the three dosage levels of the treatments. Christopher Evans, one of Genascence’s scientific founders, conducted the trial at the Mayo Clinic in Rochester, Minnesota.

The findings show no severe adverse effects from the treatments in the 12 months following injection, with one participant reporting minor fluid build-up in the knee, resolved with ice and rest. The researchers also found elevated levels of IL-1 receptor antagonist proteins in the synovial fluid of participants, who also reported less pain and better knee functions.

The CIRM award funds a new early-stage clinical trial of GNSC-001 that aims to enroll 50 individuals with osteoarthritis. Participants will be randomly assigned to receive one of two GNSC-001 dose levels or a placebo, with the study team assessing the treatment’s safety and activity in the body, as well as effects on symptoms and biomarkers of osteoarthritis.

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• Gene Therapy Stimulates Missing Enzymes in Rare Disease

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