Novel DNA plasmid therapy shows high success rate in treating chronic pain in dogs

Elenagen™, a novel DNA plasmid therapy that previously demonstrated high clinical benefit and low toxicity in cancer patients, has now shown significant promise in alleviating chronic pain demonstrating a 90% success rate. In a peer-reviewed study published in Frontiers in Veterinary Science (DOI: 10.3389/fvets.2025.1519881), Elenagen reduced osteoarthritis pain scores in companion dogs. Because the same pro-inflammatory cytokine loop drives osteoarthritis and other chronic pain states, the findings offer a promising translational signal for non opioid pain medicine. 

In the open‑label trial of 17 dogs aged 4–13 years, 90 percent achieved at least a one‑point drop in Pain Severity Score and a two‑point drop in Pain Interference Score after ten weekly intramuscular injections. Median Pain Severity fell from 5.25 to 3.25, and median Pain Interference from 7.00 to 3.27, by day 70. No treatment‑related adverse events were observed; hematology and serum chemistry remained within normal limits.

This outcome supports a mechanistic hypothesis: since chronic pain is known to result from both systemic inflammation and dysfunctional mesenchymal stem cells (MSCs)-and since Elenagen has been shown to reduce inflammation and restore MSC function-the therapy was expected to provide pain relief. The successful validation of this hypothesis may signal a potential, disease-modifying approach to treating chronic pain in both veterinary and human medicine. 

These dog data suggest we can help the body to manufacture its own multi‑modal anti‑inflammatory-without opioids or steroids. The majority of older cats and dogs suffer from osteoarthritis and the chronic pain it causes. Indeed, my four-legged family member, Sparky, is one of them. However, when I think of chronic pain, I see the faces of war veterans who survived the battlefield but did not survive the opioid addiction back home. While conducting this study, I've been thinking about them."

Dr. Alexander Shneider, founder and CEO of CureLab Oncology

How an investigational p62 plasmid may 'reset' aging stem cells and break the inflammation–pain cycle

Chronic pain affects over 20% of adults worldwide and remains a major unmet medical challenge. Existing treatments, such as opioids, are often ineffective and carry serious risks. A growing body of research identifies chronic inflammation as a key underlying cause. In young, healthy individuals, mesenchymal stem cells (MSCs) help regulate inflammation and support tissue repair. But with age and disease, these cells undergo a harmful shift-losing their regenerative function and becoming active contributors to chronic inflammation and pain conditions, including those associated with arthritis.

CureLab Oncology developed Elenagen, a circular DNA (plasmid) encoding the p62 protein. In clinical testing with platinum resistant ovarian cancer patients, Elenagen significantly extended both time to disease progression and overall survival, also demonstrating a high safety profile. In collaboration with scientists at Camerino University (Italy), the CureLab team analyzed its anticancer mechanisms and demonstrated Elenagen's broad systemic anti inflammatory effects and its ability to restore and modulate MSC function. Building on these findings, CureLab hypothesized that Elenagen could serve as an effective therapeutic for chronic pain by targeting its inflammatory root causes.

The core mechanism involves Elenagen reprogramming aged or dysfunctional MSCs. These cells, which shift toward a pro-inflammatory state and lose their regenerative capacity, are functionally 'reset' by Elenagen. Upon internalization of the plasmid, MSCs regain a youthful phenotype: they resume secreting anti-inflammatory factors and recover their ability to differentiate into functional cell types, such as osteoblasts (bone cells) rather than adipocytes (fat cells). Critically, the anti-inflammatory signals produced by Elenagen-reprogrammed MSCs travel over long distances and induce the same beneficial changes in remote MSCs as the plasmid itself-creating a system-wide amplification cascade.

Weekly p62 plasmid injections reduced limping and restored playful activity in dogs with severe osteoarthritis pain

Due to their size, natural development of chronic pain conditions such as osteoarthritis, and shared pathophysiological mechanisms with humans, dogs are considered one of the most clinically relevant translational models for studying chronic pain and testing novel therapies. In this study, dogs with severe osteoarthritis pain and limping received weekly intramuscular injections of Elenagen (1 mg). 

The results supported the hypothesis: after four doses, veterinary assessments, owner reports, and video documentation showed a marked reduction in limping and increased activity and playfulness. By six doses, most dogs exhibited near-complete improvement-limping ceased, and playful behavior returned. 

While joint structure remained unchanged, the observed functional improvement suggests that Elenagen targets pain biology directly, offering meaningful relief where structural therapies often fall short.

Significance and next steps

This pilot study provides important validation of Elenagen's novel approach to treating chronic pain. Larger, placebo-controlled trials in both dogs and humans are planned for 2026. Elenagen's well-established safety profile from prior human cancer trials significantly de-risks and accelerates its potential development pathway for pain management in both veterinary and human medicine.

Chronic pain caused by chemotherapy and other cancer treatments remains a major challenge in oncology, limiting both therapeutic options and patients' quality of life. Elenagen's potential to both delay disease progression and extend overall survival-while simultaneously reducing chronic pain-suggests a highly synergistic therapeutic profile. As a result, the company plans to incorporate chronic pain monitoring into its FDA and EMA cancer clinical trials starting in 2026.

Source:
Journal reference:

Gabai, V., et al. (2025). Efficacy of P62-expressing plasmid in treatment of canine osteoarthritis pain: a pilot study. Frontiers in Veterinary Science. doi.org/10.3389/fvets.2025.1519881.

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