A stroke is a condition where central nervous system (CNS) tissue is destroyed due to lack of blood flow and oxygenation to part of the brain. As a result of damaged neural pathways, patients experience loss of function with the disease manifestation dependent upon which region of the brain is affected. Stroke either significantly impairs the flow of blood to the brain (ischemic stroke) or it involves the rupture of blood vessels in the brain (hemorrhagic stroke). In either case, the result is the mass death of neurons which short-circuits the central nervous system (Figure 1).

Both types of strokes can result in substantial and debilitating loss of movement, senses, vision, language, speech, balance, difficulty with coordination and walking, and cognition. During an ischemic stroke, there is a mass die-off of brain cells amounting to around two million brain cells perishing every minute post-injury.

According to a report published by the World Stroke Organization in 2022, there are over 12 million new strokes each year, and there are over 100 million people currently living who have previously experienced a stroke. Of the new strokes that occur globally each year, ischemic stroke affected 7.6 million people, or about 62% of the total population who experience stroke, and hemorrhagic stroke afflicted 4.6 million, or 38% of the total population who experience stroke. For the U.S., the Center for Disease Control and Prevention (CDC) reports that every year over 795,000 people in the U.S. have a stroke, of which approximately 76% are first time strokes.¹ Interestingly, the incidence of ischemic stroke appears to be much higher in the U.S. with 87% of all strokes classified as ischemic strokes.

Of the approximately 795,000 people in the U.S. who suffer a stroke each year, only about 10% of them return to life as it was before. However, 20% of people who suffer a stroke die within a week, while another 13% die within the first year. Stroke is a leading cause of serious long-term disability and reduces mobility in more than half of stroke survivors age 65 and over.

Additionally, stroke related costs in the U.S. alone, were estimated by the CDC to be $46 billion between 2014 and 2015 (the latest figures available), a toll growing as the size of the aged population continues to expand.

Currently there is only one treatment approved for stroke, called Alteplase, or tissue plasminogen activator (tPA). Alteplase is a clot buster, and thus can only be used in patients with an ischemic stroke, which must be first confirmed by imaging. According to the FDA approved labelling, Alteplase must be administered within 3 hours of a stroke. Due to the time restrictions for starting treatment and the requirement for a brain imaging study prior to treatment, tPA is only administered to approximately 5% of patients suffering from a stroke. A key takeaway here is that no drug has ever before been approved anywhere in the world to repair or restore damage from a stroke. 

Role of brain plasticity to treat stroke

Today, the approximately 100 million stroke survivors globally have no drug treatments available to repair the damage that stroke causes. The biotechnology sector is investigating the role of neural plasticity to treat the damage caused by stroke. Improving plasticity, which repairs CNS damage, can have significant impact across multiple neurological functions, including motor and sensory. Frontiers in Cellular Neurosciences defines “neural plasticity, also known as neuroplasticity or brain plasticity, as the ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganizing its structure, functions or connections.”²

The ability to enhance plasticity is not only relevant to stroke, but also to any condition where there is damage to CNS tissue. Enhancing plasticity results from “axonal sprouting,” the process of fine nerves processing—sprouting—from the intact axons to reinnervate denervated muscle fibers. Increased plasticity (axonal sprouting) results in the creation of new neural connections and increased production of adult neuronal stem cells with enhanced migration of these cells to the site of damage.

“The ability to enable plasticity is relevant to any condition where there is central nervous system damage including Alzheimer’s disease, traumatic brain injury, spinal cord injury and multiple sclerosis,” said Dr. Jerry Silver at Case Western Reserve University who discovered a novel peptide-based innovation—NVG-291.

Dr. Silver discovered a class of molecules, called chondroitin sulfate proteoglycans (CSPGs), that are upregulated in response to nervous system damage and that inhibit repair. NVG-291 was designed to modulate the inhibitory effect of CSPGs, thereby enhancing the body’s natural repair mechanisms, including plasticity, regeneration and remyelination.

“NVG-291 offers a potential new treatment paradigm for stroke by enabling repair of the damage caused rather than trying to limit or contain the extent of the damage,” said Dr. Silver.

Stroke patients often face motor, sensory, spatial learning and memory function deficits.  Studying the role that plasticity treatment in the treatment of stroke patients to improve these functional deficits offers the potential for a completely new treatment paradigm. 

Current therapy focuses on restoring blood flow to the affected area as soon as possible in the first hours after the stroke. In contrast this potential new treatment for stroke could enable repair of damage caused by stroke rather than trying to limit or contain the extent of the damage. The ability to promote plasticity, either by promoting axonal sprouting or the migration of adult neural stem cells to repair CNS damage is a revolutionary development which would lead to a change in the treatment paradigm for stroke, while also providing a treatment option to millions of stroke victims. 

References

1. https://www.cdc.gov/stroke/facts.htm#:~:text=Every%20year%2C%20more%20than%20795%2C000,are%20first%20or%20new%20strokes.&text=About%20185%2C000%20strokes%E2%80%94nearly%201,have%20had%20a%20previous%20stroke.&text=About%2087%25%20of%20all%20strokes,to%20the%20brain%20is%20blocked
2. https://www.frontiersin.org/articles/10.3389/fncel.2019.00066/full#:~:text=Neural%20plasticity%2C%20also%20known%20as,structure%2C%20functions%2C%20or%20connections

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Paul Brennan is President and Chief Executive Officer of NervGen Pharma Corp., a publicly traded clinical stage biotech company dedicated to discovering and developing treatments for nervous system damage due to injury or disease. He can be reached at pbrennan@nervgen.com; www.Nervgen.com