Repairing Spinal Cord Injury Damage

Spinal cord injuries (SCIs) can temporarily or permanently disrupt critical functions, from sensation to breathing, contributing to substantial patient morbidities that are often lifelong. Researchers develop novel regenerative therapeutics to address a treatment gap between rehabilitation and symptom management, seeking to repair nerve damage and ultimately improve care for individuals living with SCIs.

This goal is what motivates scientists at NervGen Pharma Corporation, a clinical-stage biotechnology company dedicated to developing innovative treatments to enable nervous system repair in the settings of traumatic injury and disease. In this Innovation Spotlight, Mike Kelly, president and chief executive officer at NervGen, discusses the importance of SCI research and progressing new therapeutics from laboratory bench to clinic, including NervGen’s peptide NVG-291.

Why is it important to research SCI?

Developing treatments and technologies to restore motor function and assist people living with an SCI could reduce both the personal and systemic burden of this condition. Each year, up to 500,000 people worldwide experience an SCI and the economic burden of the injury is significant, involving high medical and personal expenses. Initial acute medical costs, including hospitalization and surgeries, can range from US$350,000 to $1 million in the first year, with ongoing medical care averaging $40,000 to $70,000 annually. Long-term costs include assistive devices, caregiver support, and potential loss of income due to the inability to work. Lifetime costs can range from $2 million to $5 million depending on the severity of the injury.

Additionally, SCI can lead to psychological challenges and social impacts, requiring mental health support. While insurance can help, many individuals face substantial out-of-pocket expenses, making SCI a major financial burden. People living with SCIs face challenges each and every day. This is what drives us at NervGen and what drives patient support organizations like Wings for Life, the Christopher & Dana Reeve Foundation, Unite 2 Fight Paralysis, Blink of an Eye®, and many others. We are all dedicated to making advancements so that one day we can help make a difference in the lives of people living with SCI.

What makes SCI difficult to treat?

Treating SCI is difficult because the spinal cord has limited ability to heal itself and damage to the spinal cord often disrupts the complex network of nerves that control movement and sensation. Nerve cells in the spinal cord do not regenerate easily and scar tissue forms quickly, blocking the regrowth of nerve fibers. Current treatments for SCI focus on managing symptoms, preventing further damage, and improving recovery. Shortly after the injury, steroid medications and surgery are used to help reduce inflammation and stabilize the spine. After this phase of treatment, physical and occupational therapy aim to improve mobility and daily function.

Currently there are no approved pharmaceutical treatments that assist in repair. Emerging therapies like stem cell treatments, gene therapy, and neuroprotective agents are being researched to promote nerve regeneration. NervGen’s approach has shown promise in overcoming these inhibitors of regrowth in several preclinical models.

What roles do chondroitin sulfate proteoglycans (CSPGs) have in the nervous system, and how is NervGen targeting these molecules to treat SCI?

Neuroscientist Jerry Silver and his research team at Case Western Reserve University made many discoveries and advancements in the field of SCI. Silver discovered that the CSPG family of molecules, suppress nervous system repair when upregulated at injury sites.¹ Building on this discovery, Silver’s lab identified intracellular sigma peptide (also known as ISP), a synthetic molecule that served as the prototype for NervGen’s NVG-291, that demonstrated the ability to counteract the inhibitory effects of CSPGs, promoting nervous system repair and functional recovery in preclinical models of SCI.²

How does NVG-291 work?

NVG-291 is a peptide that is derived from the intracellular wedge domain of the CSPG receptor protein tyrosine phosphatase sigma (PTPσ). In preclinical studies, it has been shown to interfere with CSPG signaling resulting in enhanced repair mechanisms that are normally inhibited by CSPGs, such as regeneration, myelination, and plasticity. NervGen is currently conducting pharmacokinetic, absorption, distribution, metabolism, and excretion, and exploratory omics work using samples from the ongoing clinical trials to better understand the molecular mechanism of action which is unknown.

In which stage of development is NVG-291?

NVG-291 is currently being tested for clinical safety and efficacy in a Phase 1b/2a proof-of-concept, double-blind, randomized placebo-controlled clinical trial (NCT05965700) in individuals with SCI. NervGen recently announced that enrollment in the chronic cohort (1-10 years post-injury) of the Phase 1b/2a trial has concluded, and the screening of subjects for the subacute cohort (20-90 days post-injury) of the study has initiated. We anticipate topline data for the chronic cohort in the second quarter of 2025.

What excites you the most about the future of SCI treatment?

The innovations and convergence of both science and technology are what is most exciting to address the challenges ahead of us in treating SCI. Therapeutic approaches that could potentially unlock the body’s potential to repair and reconnect nerve pathways, combined with devices and technology that can be used to accelerate converting these connections into motor function, are being studied independently today but may be combined in the future.