Breakthrough peptide repairs nerves after spinal cord injury
Spinal cord injuries have devastating consequences and impact more than 15 million people worldwide. Damage to spinal nerves can lead to pain, weakness, and even tetraplegia, where all four limbs are severely impaired. Part of the reason these injuries have no disease-modifying treatments is that nerves cannot be revived after they die – or at least, that’s what we thought.
Now, novel therapeutic modalities like gene therapies and peptides could reverse at least some of the damage for patients.
“Spinal cord injury has long been considered untreatable, but with over 15 million people affected globally and medical breakthroughs coming all the time, we now know that is no longer the case,” a spokesperson from the UK-based charity Spinal Research told BioXconomy.
One of the treatments generating buzz is NVG-291, also known as ISP, a peptide produced by the US-based pharma NervGen. The drug is based on the work of Jerry Silver, one of the most influential figures in nerve regeneration. It has shown remarkable effects both preclinically and in Phase I/II clinical trials in restoring limb function for patients.
BioXconomy sat down with NervGen CEO and physician Adam Rogers to discuss the company’s history and where he hopes to take NVG-291 from here.
Silver to gold
The origin story for NVG-291 begins at Case Western Reserve University with Silver, a professor of neuroscience who passed away in January 2025. Rogers described Silver as a renegade who “spent his entire career swimming upstream, going against the current.”
“Everyone for 100-plus years was like, ‘Once a neuron is dead, there’s no coming back.’ And here’s his lab saying, ‘Wait a second.’”
Silver’s lab showed that there was a key process that prevented neurons from coming back following injury. This process is governed by molecules found in the extracellular matrix called chondroitin sulfate proteoglycans (CSPGs). CSPGs prevent new neurons from migrating to the site of damage, so Silver’s team wondered if inhibiting them could rescue neuron repair and promote regrowth.
That led them to develop a peptide they called intracellular sigma peptide (ISP) – the drug that would go on to become NVG-291.
[Silver’s] relentless pursuit of innovative therapies transformed hope into tangible progress for those affected by spinal cord injuries.
The Case Western team published a landmark Nature paper where they demonstrated that the 35-amino-acid ISP could inhibit CSPGs and treat spinal cord injury animal models. This set the stage for a slew of follow-on papers that eventually led to Silver’s involvement as an advisor to NervGen.
Silver’s contributions are recognized throughout the field. The Spinal Research spokesperson referred to his work as “groundbreaking,” adding that his “relentless pursuit of innovative therapies transformed hope into tangible progress for those affected by spinal cord injuries.”
Rat rescue
Silver and his colleagues’ work with animal models of spinal cord injury laid out a compelling case for human trials. They found that injecting ISP subcutaneously into the abdomen of rodents had dramatic effects on functional outcomes.
“[Rats in] the placebo arm do not improve,” Rogers explained. “They drag their hind legs, their tails are depressed. In the treatment arm, you get about a 60–80% response rate where you see these animals; their hind legs are functioning, their tail is elevated, their rump is elevated, and they can walk across a wooden board. You really see a return to near-normal hind function and elevation of the tail.”
Rogers added that the effect could be seen on the cellular level. Delivering ISP helped neurons grow past the CSPGs to help restore function to the limbs, bladder, and diaphragms of the rats. The results of Silver’s efforts were published in Nature Communications, Journal of Neurotrauma, and others.
The fact that ISP could be delivered efficiently with a subcutaneous injection was a big part of the attraction for Rogers, who joined the company first as an investor and advisor before becoming CEO.
“The fact that you can give this as a subcutaneous injection where someone can go home, store this in their freezer or their refrigerator, and inject it into their belly or their arm or their thigh – no different than you would do with GLP-1 drugs – it lowers the barrier,” he said.
Peptides meet patients
When NervGen licensed the ISP patents, it rebranded the peptide to NVG-291 and brought it into human tests. The company’s Phase I clinical safety trial (NCT05308953) closed in 2023, while its Phase Ib/IIa trial (NCT05965700) for NVG-291 wrapped up in late 2025/early 2026.
“We didn’t know what we were going to get out of this [Phase II] study,” Rogers said. “We figured at a minimum, we would get an improvement in electrical impulse.”
“So far, the functional impact that we’ve seen in these individuals is really phenomenal.”
He said the results from the trial surpassed their expectations. Reflecting the remarkable results NervGen saw in animal models, trial participants experienced dramatic positive changes after receiving the treatment. Rogers also said this included improvements in electrical impulses in patient limbs, suggesting nerve function had been restored.
The team measured functional outcomes using the GRASSP (graded redefined assessment of strength, sensibility, and prehension) system, which tests fine motor skills like putting a lock into a key and turning it.
“What we found at 12 weeks in was that the ten individuals that received drugs had a 3.7-point improvement in GRASSP quantitative prehension,” Rogers said. “What does this improvement mean to the average person? The ability to brush your teeth, button your shirt, comb your hair, open a water bottle, zipper up your pants – day-to-day activities.”
The prospect of giving patients the ability to become more self-reliant so that they can “transfer from one chair to another” or “make a meal on their own” represents a sea change for those with spinal cord injuries.
Perhaps even more exciting than the initial results was the fact that participants reported benefits one year after stopping the drug, according to blinded qualitative exit interviews.
“When you interview these individuals almost a year out from the study, those individuals that received the drug, their report was, ‘Look, I stopped the drug and I continued to see a stepwise improvement over the 259 days on average after I discontinued it.’”
He added that five of the participants even made appearances on local news stations.
“When you see their interviews, while it’s not within the guise of a clinical trial, you can see that these individuals are maintaining improvements that they’ve had,” Rogers said. “We’ll obviously have to test that in future studies.”
Just days before more positive news dropped about the outcome of their Phase II trial, NervGen went public on May 21 with a public offering of $60 million.
Now and again
One of the perennial barriers in peptide therapeutics is sustainability. Manufacturing peptides requires the use of harsh solvents with significant environmental effects. Questions around these CMC practices have come under scrutiny with the meteoric rise of GLP-1s, which have to be dosed repeatedly to maintain their effect.
Rogers told us that for now, the company is focused on the discovery side and relying on external companies for CMC support.
“We hire CDMOs [contract development and manufacturing organizations] within the United States to manufacture it. Obviously we’re not going to be making it at the level of GLP-1.”
As for whether sustainability questions have come up for the team so far, Rogers demurred.
Many of these individuals cannot work. […] They are being readmitted to the hospital for a variety of different reasons – bladder infections, pressure sores, you name it.
“We have not explored that at this point in time,” he said. “Our mission here is to get a drug across that’s going to improve the lives of individuals with spinal cord injury.
“It’s a massive market. It’s a group of individuals that want improvement function and have a lot of hope. And that’s our mission, really: to bring hope to those individuals to improve their function.”
The other important question for any new therapeutic concerns affordability. Rogers framed NervGen’s approach in the context of the personal and communal economic costs of spinal cord injury.
“The question is, what is the impact on someone’s life with spinal cord injury?” he said. “Many of these individuals cannot work. They’re at home. They need home health care. They are being readmitted to the hospital for a variety of different reasons – bladder infections, pressure sores, you name it.”
“From an economic and societal burden, there is up to an $8.3 million lifetime cost per patient.”
He said this amounts to a “$58 billion hit” on US healthcare.
“If we can get an individual where they can use a mouse or use a keyboard and they can communicate with their office, they can then work and they have a positive impact on the economy of the United States.”
Rogers added that he does not foresee NVG-291 being a drug that patients take for the rest of their lives, limiting the long-term investment.
“In this capacity of spinal cord injury, I believe that they will take a number of rounds of [NVG-291],” he said. “And then likely when they hit the ceiling, they’ll likely discontinue the drug.”
“Our mission is to bring a drug to market to help individuals. That’s why I got involved in this company,” Rogers said. He initially joined NervGen as an investor in 2022 before becoming CEO in July 2025. “I didn’t get involved for financial gain.”
Expanding scope
The NervGen team is actively preparing for its Phase III trial. Rogers said they plan to start their study in mid-2026.
He anticipates their peptide could play a role in other conditions where neuronal death prevents therapeutic intervention, like Alzheimer’s, amyloid lateral sclerosis (ALS), and stroke.
“This is not just a spinal cord injury drug and we are not just a spinal cord injury company,” he emphasized. “I look at us as a neurotraumatic company and a neurodegenerative company. To pigeonhole us just in the spinal cord injury is very limiting.”
Meanwhile, Spinal Research sees a range of medicines like NVG-291 on the horizon that it anticipates helping patients in previously unimaginable ways.
The next five years present an unprecedented opportunity to change what’s possible for people living with spinal cord injuries.
“Breakthrough therapies are moving closer to reality, and new technologies are helping researchers move faster than ever before. Spinal Research is leading this effort to turn hope into recovery with the launch of our Recovery Alliance,” the spokesperson said. “This brings researchers, industry partners, funders, clinicians, and the spinal cord injury community together to help accelerate discoveries and get them to the people who need them at speed and scale.”
“Until very recently it was thought that a spinal cord injury was incurable,” Spinal Research CEO Louisa McGinn told BioXconomy. “But breakthrough therapies are nearing clinical reality and frontier technologies, from AI and robotics to gene therapies, are creating bold new pathways toward repair and recovery.
“We are entering a new era of possibility and hope and, if we can generate the funding, the next five years present an unprecedented opportunity to change what’s possible for people living with spinal cord injuries,” she concluded.
Quotes have been lightly edited for clarity. This article was updated on July 8, 2026, to reflect the financial burden of $58 billion and to clarify that ISP was licensed by NervGen.
