NVG-291 for spinal cord injury

An experimental drug could help to improve movement for patients with spinal cord injuries.

NVG-291, an injectable peptide, has been tested in a phase 2 trial with eligible patients — some of whom noted remarkable outcomes.

Larry Williams, a trial participant based in Philadelphia, Pennsylvania, shared with Fox News Digital that he’s been able to walk again after an accident that caused paralysis.

Williams, 58, was mountain-biking on a small trail when he struck a tree. Although he was wearing a helmet, he "instantly broke" his C4 to C6 vertebrate (specific bones in the cervical spine).

He underwent spinal surgery, but was paralyzed for two weeks until his body began to "wake up" and regained some movement after starting therapy.

Williams was able to walk "a little bit" with the assistance of a walker, but still had complications with mobility in areas like his hands. He also lost 40 pounds after the accident.

After some research, he discovered the NVG-291 trial and was considered a viable candidate, he told Fox News Digital.

For three months, starting in April 2024, Williams received a daily injection of the drug followed by one hour of physical therapy, which included hand exercises and walking with a harness on a flat track or treadmill.

Williams also underwent blood tests and electrophysiological testing to measure the electrical activity of his nerves and muscles, as well as physical testing once a month.

At the end of the trial, Williams reported that he was able to walk 10 meters (32.8 feet), balanced with a walker, in 15 seconds, an improvement over 45 seconds.

Although he has not received the drug since July 2024, Williams continues to see physical improvements over a year later.

"I'm not working out really hard. I'm currently not in therapy," he told Fox News Digital. "But just a couple of days ago, I stood up and tried to free-stand, balance and lift one foot off the ground. I was able to do it for 30 seconds."

"I hadn't been practicing this. I can't explain how it happened," he added. "There are small improvements that continue to happen."

Williams said he had tried the same maneuver six months earlier and couldn’t hold his foot off the ground for even three seconds.

"There are small improvements that continue to happen."

Since the trial, Williams has continued to improve his walking ability, and can even swim laps in the pool.

"I reach out to other people with the same injury as me, and it seems like a lot of them, after years and years of therapy, get to where I am," he said. "And it kind of seems like I've been given a shortcut … I would love to get to the life that I had before, being fully independent."

After taking the experimental drug, Williams said he has been able to perform physical tasks "easily and quickly."

"The movement in my legs seems to be a little bit smoother and less restricted as the time passed by," he said. "I'm not going to give up. I'm going to keep pushing and trying."

How the drug works

In a separate interview with Fox News Digital, lead researcher Dr. Monica Perez, scientific chair at the Shirley Ryan AbilityLab in Chicago and professor of physical medicine and rehabilitation at Northwestern University, said the drug was first tested on animals, which displayed improved locomotor function (movement).

The researchers then conducted a randomized clinical trial in humans, in which half of the participants received the NVG-291 drug, which contained a repair molecule to improve nervous system function.

The drug is a peptide, which is a small protein that works like a roadblock remover. After a spinal cord injury, the body sends out signals that tell nerve fibers to stop growing. This drug blocks those signals, so the nerves have a better chance to regrow.

"This peptide can block those inhibitory signals," Ryan said. "There is a little bit of evidence in animals that it can actually enhance the growth of neurons."

Although GLP-1 receptor agonists, best known for weight loss and diabetes treatment, are a peptide, Perez said this spinal cord injury treatment works differently.

"It has a specific mechanism, and it's more related to repair, to try to enhance the growth of neurons that are affected by central nervous system injury," she said.

Spinal cord injuries are typically approached with cell therapies, like stem cells and bone marrow stromal cells, Perez noted.

This peptide approach, in contrast, is "easy to administer," can be done at home, achieves a "similar goal" and is "extremely safe," she added.

Perez said more research is necessary to determine how long the effects of this drug will last.

"We observed strong electrophysiological changes in the group that received the medication compared to the placebo group, but we don't have follow-up measurements," she said. "There's no way for us to understand the real duration of these treatments."

As there is not currently an FDA-approved treatment for spinal cord injuries, Perez said that those involved with this research are "very devoted" to advancing this science.

While each patient may react differently, Williams said he would recommend this treatment to other people with spinal cord injuries.

"It could really change things for people with injuries like mine," he said. "I'm just praying that everybody out there is able to have an opportunity to gain back their life."

Angelica Stabile

https://www.foxnews.com/health/paralyzed-man-walks-again-after-experimental-drug-trial-triggers-remarkable-recovery

Daniel Mikol, Judy Toews, Steven Mulcahy, Marc DePaul, Nana Collett, James Guest, Monica Perez. NVG-291 Phase 1 Results and Phase 1b/2a Study Design in Individuals with Spinal Cord Injury, Archives of Physical Medicine and Rehabilitation, Volume 105, Issue 4, 2024, Page e18, ISSN 0003-9993, https://doi.org/10.1016/j.apmr.2024.02.049.

Research Objectives
To provide an update on the development of NVG-291 for spinal cord injury (SCI). There is a high unmet need for treatments to repair damage after SCI. A Phase 1 safety trial of NVG-291 (a receptor protein tyrosine phosphatase sigma peptide mimetic) in 70 healthy subjects supports a Phase 1b/2a efficacy/safety trial in individuals with SCI. Doses tested overlap with and exceed equivalent efficacious doses in animal models of acute/chronic SCI.

Design
The 16-week Phase 1b/2a randomized, double-blind, placebo-controlled trial (12-week treatment period, 4-week noninterventional period) will assess individuals with chronic and subacute traumatic SCI.

Setting
The trial will be conducted at a single center, Shirley Ryan AbilityLab (Chicago, IL). We will conduct longitudinal electrophysiological assessments to enable precise measurement of descending motor connectivity following treatment.

Participants
Approximately 40 subjects will be enrolled. ∼20 cervical motor incomplete SCI subjects per cohort will be enrolled: cohort 1 chronic (1 – 10 years post-injury); cohort 2 subacute (10 – 49 days post-injury). All subjects will undergo regular exercise.

Interventions
Randomization (1:1) to NVG-291 or placebo (daily subcutaneous injection) for 12 weeks.

Main Outcome Measures
The primary objective is to evaluate the change in motor evoked potential amplitudes (an index of corticospinal excitability) in predefined muscle groups. Other electrophysiological measures will also be assessed. Key clinical outcome measures include 10mWT, 9-HPT, GRASSP, pinch dynamometry, and motor scores.

Results
NVG-291 was safe and well tolerated in the Phase 1 trial and showed good pharmacokinetic characteristics. The most common AE was injection site related, more common in the NVG-291 group.

Conclusions
Phase 1 results support advancing investigation of NVG-291 to individuals with SCI. The Phase 1b/2a trial in SCI, which initiates in mid-2023, will assess change in electrophysiological and clinical measures following treatment of individuals with subacute or chronic SCI.