A new study has unveiled a molecule that could transform how we treat strokes and prevent related brain damage. The international research team, co-led by scientists from The Hospital for Sick Children (SickKids) and Shanghai Jiao Tong University School of Medicine, has identified a compound called LK-2 that shows promise in protecting brain cells during a stroke.
Ischemic strokes, caused by interrupted blood flow to the brain, deprive cells of oxygen and nutrients, leading to potentially permanent damage. As one of the leading causes of death and disability worldwide, finding effective treatments for stroke is crucial.
Dr. Lu-Yang Wang, Senior Scientist at SickKids and co-leader of the study published in Nature, explains: “Our findings provide an entirely new way to think about saving cells while minimizing the adverse neural side effects of conventional stroke therapy. The LK-2 molecule could be the key to unlocking successful therapeutics for stroke patients.”
Glutamate: The Double-Edged Sword
During a stroke, levels of the neurotransmitter glutamate rise dramatically in the brain. This excess glutamate overstimulates receptors on brain cells, causing a surge of calcium that leads to cell death. Previous attempts to block these receptors, called N-methyl-Daspartate receptors (NMDARs), have failed due to their importance in normal brain function.
The research team discovered that glutamate also activates another type of receptor called acid-sensing ion channels (ASICs). “We have shown that glutamate can supercharge the activity of ASICs, especially under the acidic conditions that occur during stroke,” Wang explains. “This means that glutamate is attacking brain cells through both NMDARs and ASICs – something we did not know before now.”
LK-2: A Targeted Approach
By identifying the specific site where glutamate binds to ASICs, the team developed LK-2, a molecule that can selectively block this binding site without affecting NMDARs. In preclinical models, LK-2 effectively reduced calcium flow and cell death by preventing glutamate from overstimulating ASICs.
Crucially, LK-2 did not interfere with normal neural transmissions, suggesting its potential as a next-generation stroke treatment. “Our research has revealed a new way to protect the brain from glutamate toxicity without interfering with NMDARs,” Wang states.
This discovery could lead to more effective stroke treatments with fewer side effects than current therapies. By targeting ASICs specifically, LK-2 avoids the pitfalls of previous attempts to block glutamate’s damaging effects.
The research team plans to continue exploring LK-2’s function and mechanisms, with the goal of developing future clinical trials. If successful, this new approach could significantly improve outcomes for stroke patients, potentially saving lives and reducing long-term disability.
As stroke remains a major global health concern, the development of LK-2 represents a promising step forward in our ability to protect the brain during these critical events. While more research is needed to bring this treatment to patients, the discovery opens up new avenues for stroke therapy that could benefit millions worldwide.
