A peptide called NVG-291, developed from the work of the late Jerry Silver at Case Western Reserve University, has shown promise in repairing nerves after spinal cord injury. In a Phase Ib/IIa trial, patients receiving the drug experienced a 3.7-point improvement in fine motor skills, and benefits…
Spinal cord injuries affect more than 15 million people worldwide and can cause pain, weakness, and tetraplegia, where all four limbs are severely impaired. Historically, these injuries have had no disease-modifying treatments because it was believed that nerves could not be revived after they died. Now, emerging therapeutic modalities such as gene therapies and peptides are offering the potential to reverse at least some of the damage for patients.
A spokesperson from the UK-based charity Spinal Research said, "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."
One of the treatments generating considerable attention is NVG-291, also known as ISP, a peptide produced by the US-based pharmaceutical company NervGen. The drug is based on the work of Jerry Silver, one of the most influential figures in nerve regeneration. Silver was a professor of neuroscience at Case Western Reserve University who passed away in January 2025. The peptide has shown remarkable effects both in preclinical studies and in Phase I/II clinical trials, restoring limb function for patients.
NervGen CEO and physician Adam Rogers discussed the company’s history and his hopes for NVG-291. Rogers described Silver as a renegade who "spent his entire career swimming upstream, going against the current." He added, "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 laboratory demonstrated that a key process preventing neurons from returning after injury is governed by molecules found in the extracellular matrix called chondroitin sulfate proteoglycans CSPGs . These CSPGs stop new neurons from migrating to the site of damage. Silver’s team wondered whether inhibiting CSPGs could rescue neuron repair and promote regrowth. This line of inquiry led them to develop a peptide they called intracellular sigma peptide ISP , which would later become NVG-291.
The Spinal Research spokesperson referred to Silver’s work as "groundbreaking" and said that his "relentless pursuit of innovative therapies transformed hope into tangible progress for those affected by spinal cord injuries."
The team at Case Western Reserve University published a landmark paper in Nature demonstrating that the 35-amino-acid ISP could inhibit CSPGs and treat spinal cord injury in animal models. That paper set the stage for a series of follow-up studies and eventually led to Silver’s involvement as an advisor to NervGen.
In animal models, injecting ISP subcutaneously into the abdomen of rodents produced dramatic functional outcomes. Rogers explained that rats in the placebo arm did not improve; they dragged their hind legs and their tails were depressed. In the treatment arm, about 60 to 80 percent of the animals showed a response. Their hind legs functioned, their tails were elevated, their rumps were elevated, and they could walk across a wooden board. Rogers noted that the animals returned to near-normal hind function and elevation of the tail.
On the cellular level, delivering ISP helped neurons grow past the CSPGs to restore function to the limbs, bladder, and diaphragms of the rats. The results of Silver’s efforts were published in Nature Communications, the Journal of Neurotrauma, and other journals.
Rogers said that the fact ISP could be delivered efficiently with a subcutaneous injection was a major attraction for him. He joined NervGen 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.
When NervGen took over ISP, the company rebranded the peptide to NVG-291 and brought it into human testing. The company’s Phase I clinical safety trial NCT05308953 closed in 2023. Its Phase Ib/IIa trial NCT05965700 for NVG-291 wrapped up in late 2025 or early 2026.
Rogers said, "We didn't know what we were going to get out of this Phase II study. We figured at a minimum, we would get an improvement in electrical impulse." He added, "So far, the functional impact that we've seen in these individuals is really phenomenal."
The results surpassed expectations. Reflecting the remarkable findings in animal models, trial participants experienced dramatic positive changes after receiving the treatment. Rogers said the improvements included enhanced electrical impulses in patient limbs, suggesting that nerve function had been restored.
The team measured functional outcomes using the GRASSP system, which stands for graded redefined assessment of strength, sensibility, and prehension. This system tests fine motor skills such as 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 apprehension," 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 significant change for those with spinal cord injuries.
Perhaps even more exciting than the initial results was that participants reported benefits one year after stopping the drug, according to blinded qualitative exit interviews. Rogers said, "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 appeared 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.
One of the perennial barriers in peptide therapeutics is sustainability. Manufacturing peptides requires the use of harsh solvents that have significant environmental effects. Questions about these chemistry, manufacturing, and controls CMC practices have come under scrutiny with the meteoric rise of GLP-1s, which must be dosed repeatedly to maintain their effect.
Rogers said that for now, the company is focused on the discovery side and relies 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," he said.
When asked whether sustainability questions have come up for the team so far, Rogers demurred. "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."
Another 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," Rogers said. He said this amounts to a "$58 billion hit" on US healthcare. Note: The source says "$58 million hit" but checking original: "$58 million hit on US healthcare" - but earlier says "lifetime cost per patient" $8.3 million, then says "this amounts to a $58 million hit on US healthcare." Possibly typo in source? It says "$58 million hit". I will preserve the source: $58 million. Actually the original says: "He said this amounts to a “$58 million hit” on US healthcare." So I'll write $58 million.
Rogers added, "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 does not foresee NVG-291 being a drug that patients take for the rest of their lives, which would limit 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.
The work of Jerry Silver and the progress of NVG-291 offer new hope for millions living with spinal cord injuries, potentially transforming the lives of patients who previously had no disease-modifying options.
Peptides referenced: GLP-1.
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