Spinal cord injuries (SCI) are devastating medical conditions, often resulting in permanent loss of sensory and motor functions, and no treatment was found yet. However, promising candidates like Lineage Cell Therapeutics’ OPC1 and NervGen’s NVG-291 are currently in the pipeline, offering hope for future therapeutic options. Mike Kelly, chief executive officer (CEO) of NervGen explained how the burden of spinal cord injury (SCI) remains significant on medical, economic, and social fronts.
“Each year, around 500,000 people worldwide suffer from spinal cord injury, which imposes a tremendous physical, emotional, and economic burden. A single patient may face lifetime care costs ranging from $1 million to $4 million, depending on the severity and age at the time of injury.”
Beyond financial strain, spinal cord injury significantly diminishes the quality of life.“Tragically, many individuals experience a loss of mobility and must quickly adapt to living with impairments,” added Kelly.
The traditional approach to treating these injuries has remained largely focused on rehabilitation and physical therapies that aim to optimize whatever residual function remains. However, these treatments don’t directly address the root causes of nerve damage, such as the loss of axons or the breakdown of neural circuits.
Despite decades of research and some advances, there is no treatment for spinal cord injury. Brian Culley, CEO of Lineage – another company addressing spinal cord injury – described the current landscape as “almost depressing” but he remains optimistic.
“For now, it looks like poor soil but there are pockets of progress that are really encouraging. To be optimistic about it shows there’s a clear unmet need and a tremendous opportunity to positively affect people suffering from spinal cord injury.”
In recent years, scientists and biotech companies have turned to regenerative medicine to find better solutions.
One promising direction in this space is cell therapy, exemplified by Lineage Cell Therapeutics and its investigational product OPC1. Alongside, another innovative approach is NervGen’s NVG-291, working to illicit the molecular mechanism of action of the protein tyrosine phosphatase sigma (PTPσ) to remove the natural barriers that inhibit nerve regeneration, paving the way for the body to heal itself.
Let’s take a closer look at what might be the future of spinal cord injury.
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Regenerating the spinal cord through cell therapy with Lineage’s OPC1
Cell therapy has emerged as a promising tool for treating spinal cord injuries aimed at promoting axonal regeneration and motor recovery. It involves the transplantation of cells that can directly support the repair of damaged tissues.
Lineage Cell Therapeutics has taken a unique approach using oligodendrocyte progenitor cells (OPCs) to treat spinal cord injury. Its investigational product, OPC1, is designed to promote motor recovery in patients with spinal cord injuries by transplanting these precursor cells into the injury site.
“OPCs are the myelinating cells that naturally exist in the spinal cord, meaning they’re key to carrying the electrical signal and, thus key to mobility. Our approach consists of taking cells that have been destroyed in the accident and providing functional oligodendrocyte cells to replace them and restore the activity in the spinal cord. It is different from stem cell therapy where we might utilize an undifferentiated stem cell, these are differentiated cells,” explained Culley.
In a phase 1/2a clinical trial involving 25 patients, OPC1 was shown to provide functional improvements, particularly in upper extremity motor functions. “The initial study involving 30 patients to date (five in phase 1 and 25 in phase 1/2a) has been encouraging in terms of efficacy and also safety but we ultimately need to demonstrate that in a larger and controlled clinical study.”
While cell therapy holds great promise for spinal cord injury, several challenges remain.
“Most of the challenges are pretty common. More specifically on spinal cord injury, I think what makes it challenging is neuroregeneration itself, the central nervous system isn’t wired to repair itself like the skin. Also, there haven’t been hundreds of attempts to have therapeutic interventions for spinal cord injury so there’s not a lot of reference data. So as an industry, we are going to have to find relevant endpoints and navigate an unknown regulatory landscape. But it does allow companies like us to drive this process together with the U.S. Food and Drug Administration (FDA),” said Culley.
Molecular Inhibition: A promising approach with NervGen’s NVG-291
Protein tyrosine phosphatase sigma (PTPσ) is a receptor that plays a role in inhibiting nerve regeneration following spinal cord injury. When spinal cord damage occurs, chondroitin sulfate proteoglycans (CSPGs) accumulate at the injury site, creating scar tissue that inhibits axonal regrowth and prevents natural nerve regeneration. “By mitigating these inhibitory effects, we aim to promote nervous system repair,” said Kelly.
Indeed, NVG-291, developed by NervGen, has been shown in preclinical models to improve functional outcomes by enhancing remyelination, axonal regeneration, and neuroplasticity.
“Our NVG-291 technology stems from a discovery in the lab of Dr. Jerry Silver at Case Western Reserve University. His team identified a synthetic molecule (ISP) that served as the prototype for NVG-291, which was shown to counteract the inhibitory effects of CSPGs and promote nervous system repair,” explained Kelly.
NVG-291 reactivates critical regenerative processes, including axonal regeneration, remyelination, and enhanced neuroplasticity. These processes are vital for repairing nerve damage and restoring lost functions in patients with spinal cord injuries. At this point, NervGen is still conducting confirmatory studies on the exact molecular mechanism of action, but the technology is promising.
“While many traditional approaches focus on physical rehabilitation, neuroprotective agents to reduce secondary injury, or gene therapies to promote nerve growth, they typically aim to enhance overall growth without significantly advancing regeneration. NVG-291 presents a tremendous opportunity as a drug candidate specifically targeting regeneration and plasticity within the central nervous system,” added Kelly.
NVG-291 was found to be well tolerated across all single and multiple doses with no treatment discontinuations or serious adverse events in phase 1 clinical trial.
“Now, we are conducting a phase 1b/2a clinical study of NVG-291 in individuals living with spinal cord injury. This trial is going well, and we anticipate completion of enrollment in the first cohort of patients with chronic SCI soon. It is a 16-week trial, so we expect results shortly after the last patient completes the study. After we review the data, our goal is to have an end-of-phase 2 meeting with the FDA and advance NVG-291 forward to the next phase of development,” declared Kelly.
Cell therapies like OPC1 aim to directly replace the damaged cells responsible for remyelinating the spinal cord and restoring function. In contrast, NVG-291 reactivates dormant regenerative pathways within the patient’s own cells, enabling the body to heal itself.
Kelly said the market for NVG-291 is significant as for now there is no pharmaceutical treatment for spinal cord injury. “We do not foresee many commercial challenges if approved, the challenges are limited to demonstrating clinical success,” he said.
If both NVG-291 and OPC1 advance smoothly through the clinic, there might finally be a pharmaceutical solution for spinal cord injury patients.
Future outlook of the spinal cord injury landscape
It is clear that spinal cord injury is an area of unmet need and these two different approaches could offer hope to patients suffering from the condition. But both CEOs we talked to agreed spinal cord injury was to be addressed in a transindustrial way.
“Although our current focus is to see success as a monotherapy, we certainly see a significant opportunity to combine treatments, devices, and other technologies in the spinal cord injury space. There are several cutting-edge technologies such as exoskeletons and other approaches because spinal cord injury is such a complex challenge to solve. Like many areas of unmet needs, multiple new technologies advance the field and bring comprehensive new protocols and solutions to challenging problems,” said Kelly.
Culley agrees that the collaborative approach between industries is important to ease the patients’ burden and according to him, the slightest improvement in mobility can make a significant difference in a patient’s life.
As both Culley and Kelly pointed out, the nervous system has a natural repair process that is limited by complex biological mechanisms, making it difficult to develop drugs that can effectively support nervous system repair in spinal cord injury.
“Similar to the blood-brain barrier, the blood-spinal cord barrier restricts the passage of drugs into the injured spinal tissue. Designing drugs that can effectively cross or have an effect beyond this barrier and reach the site of injury is a key obstacle,” said Kelly, indicating there is still a long way to go.
While this condition still hasn’t found any pharmaceutical treatment, some innovative approaches might be on the brink of a breakthrough.