Road to Nervous System Repair Inspired by 20th Century Nobel Prize Winner

In 1906, Camillo Golgi and Santiago Ramón y Cajal received a Nobel Prize in Medicine “in recognition of their work on the structure of the nervous system.”

As one of the founding fathers of modern neuroscience, Dr. Santiago Ramón y Cajal challenged generations of neuroscientists with his judgment on neural regeneration. He stated, “In adult centers the nerve paths are something fixed, ended, immutable. Everything may die, nothing may be regenerated. It is key for the science of the future to change, if possible, this decree.”

Dr. Cajal believed that when nerves are injured, they do not regenerate. This decree translates to people with spinal cord injury whom he believed would never regain movement in paralyzed regions. It applies to those afflicted with Alzheimer’s with no route to reversing cognitive decline. Or the person with multiple sclerosis who would never find a pathway to reverse damaged neurons that impair signal transmission.

Further, Dr. Cajal believed that if this problem could be solved, it would be due to the great efforts of scientists in a future generation.

A future generation of scientists a century later took up Dr. Cajal’s call to arms and sought to counter his dire prognostication on the prospect of nerve regeneration. In 2023, we have the promise of the world’s first drug candidate that may be able to unlock the central nervous system’s natural ability to repair itself.

Known as NVG-291, this novel experimental compound just overcame a major hurdle that enables it to now be tested for the first time in humans suffering from nervous system damage.  My company, NervGen Pharma Corp., announced its successful completion of dosing of all healthy volunteers in its Phase 1 clinical (safety) trial.

In this Phase 1 trial, healthy subjects were injected daily with this novel compound subcutaneously (under the skin) for up to 14 days. While the safety data from the final cohorts of subjects remain blinded, all subjects completed dosing with NVG-291, and there were no serious adverse events in subjects receiving NVG-291.

This means that we plan to initiate a Phase 1b/2a trial in individuals with spinal cord injury as early as Q3 this year. Encouraging results from preclinical studies with NVG-291 have led us to evaluate two groups of individuals – one with a chronic injury (1-10 years post-injury) and one with a subacute injury (10-49 days post-injury).

In preclinical studies, NVG-291-R has been demonstrated to promote the recovery of various functions, such as locomotion and bladder control, by enabling repair mechanisms in the nervous system, including axonal regeneration, remyelination and enhanced plasticity.

In terms of the Big Picture, the potential impacts for NVG-291 are especially profound if the upcoming trial in spinal cord injury demonstrates effectiveness, in which case the company will pursue a larger, and possibly pivotal, trial of NVG-291. If the later-stage trial(s) demonstrate safety and meaningful efficacy of NVG-291, this could pave the way for a new drug application and eventual commercial approval.

Moreover, success in spinal cord injury may have much broader implications. If NVG-291 can promote repair of the nervous system in individuals with spinal cord injury, it may support testing NVG-291 in other conditions associated with central nervous system damage, including Alzheimer’s disease, multiple sclerosis and stroke.

In short, NVG-291 is now vying to be the first drug that can repair damage to the central nervous system.

Leveraging off a solid scientific foundation 

NVG-291 is the result of several decades of research conducted by a renowned neuro-researcher. Dr. Jerry Silver is a professor at the Department of Neurosciences, School of Medicine, at Case Western Reserve University.

Dr. Silver first came to global prominence in The New York Times in an article entitled, “Rat Nerves Repaired and Rejoined With Spine” which chronicles the first time crushed nerves were repaired. The compound Dr. Silver invented goes beyond spinal cord repair to promote functional recovery and enable nervous system repair in a range of animal models, including models of spinal cord injury, peripheral nerve injury, multiple sclerosis and stroke, through enhanced plasticity, axonal regeneration and remyelination.

Dr. Silver's laboratory in Cleveland, Ohio, along with other academic institutions and partners, has dedicated an extraordinary amount of time and energy to advance and evolve the core technology of NVG-291. This technology targets a class of molecules called chondroitin sulfate proteoglycans (CSPGs) that accumulate at sites of central nervous system damage. Dr. Silver's invention was inspired by his discovery that CSPGs inhibit the natural ability of the nervous system to repair itself. His scientific contributions have been recognized with prestigious awards, including The (Christopher) Reeve-Irvine Medal.

CSPGs are prevalent at sites of nervous system damage, whether it be the result of a spinal cord injury, stroke, multiple sclerosis or in the brain of those suffering from Alzheimer’s disease.

By unlocking the secret of how CSPGs inhibit repair, Dr. Silver laid the groundwork for creating NVG-291. Not only has this drug candidate been shown to regenerate damaged neurons in animal studies, but it has also shown to create entirely new connections between neurons, which is known as “plasticity”.

In so doing, the remaining neurons are able to amplify their functionality as much as ten-fold, according to Dr. Silver.

Dr. Silver states: “If we can prove that we can get NVG-291 into the brain and spinal cord, then it is going to do some magical things. We have already seen that being achieved in our animal models. When we start injecting people, we are hoping to see them actually recover.”

Dr. Silver says he takes heart from his scientific findings and the considerable encouragement that they may offer individuals with spinal cord injuries, as there are currently no drug treatments available to enable any recovery of function.

He states: “I believe we can replicate what we have achieved in preclinical studies with laboratory rodents. Especially considering that human beings have surprisingly similar physiologies to these animals. If we are able to see similar recovery outcomes with humans, that would be remarkable. I am confident that our research shows we are on the right track.”

Rebutting Dr. Cajal’s decree would alleviate human suffering for the thousands of patients who experience a spectrum of neurological disorders for which little can be done.

Imagine a time when paralyzed people can regain lost function or when people with neurodegenerative diseases finally have access to a drug that promotes repair and improves function? 

About the author:

Bill Radvak is Executive Chairman and Interim Chief Executive Officer of NervGen Pharma Corp., a publicly traded clinical-stage biotech company dedicated to developing innovative treatments that enable the nervous system to repair itself following damage, whether due to injury or disease. He can be reached at bradvak@nervgen.com.