New drug patented for preventing brain damage after a stroke
The American Stroke Association has been running an advertisement lately in my neighborhood that reads, “Learn to recognize a stroke, because time lost is brain lost.” The campaign is part of an effort to educate people about the warning signs and dangers of strokes. Strokes are a type of ischemia, or restriction in blood supply, that may be caused by a disruption in blood flow to the brain due to a clot or a leak in a blood vessel. The disruption deprives the brain of oxygen, often resulting in localized death of brain tissue. Thus, with each moment that the brain is deprived of oxygen, more brain cells are permanently damaged. This damage may result in partial facial or body paralysis, loss of speech, blindness or death.
The more rapidly the blood clot causing the stroke is cleared and blood flow is returned to the brain, the less brain cells will die. Currently offered medications, such as the drug tPA (tissue plasminogen activator), may help to clear these blockages, but are only recommended for treatment within three hours of the onset of symptoms. This narrow window is clearly problematic for those living in more remote areas, or for those stroke victims who aren’t aware that they’ve suffered a stroke or who have lost consciousness.
A new patent, assigned to the Morehouse School of Medicine and partially sponsored by the National Institutes of Health, seeks to deal with this temporal issue with a new pharmaceutical for treating ischemia. The patent claims a method comprising administering a therapeutically effective amount of an acid sensing ion channel 1a (ASIC1a) inhibitor to an ischemic subject to reduce injury resulting from the stroke. This inhibitor may be administered nasally, epidurally or intrathecally, meaning in the space under the erachnoid membrane of the brain or spinal cord. This administration may occur at least two hours and up to twenty-four hours after the stroke, thereby giving patients a broader window of time for treatment.
The invention is founded on the contention that changes in the ion flux into neurons may lead to the cell death produced by the stroke. Excessive calcium ions in the cell may activate a cascade of cytotoxic events leading to activation of enzymes that break down proteins, lipids and nucleic acids. Furthermore, oxygen depletion during ischemia may force the brain to switch to anaerobic glycolysis, thereby causing a buildup of lactic acid as a byproduct of glycolysis. The protons produced by ATP hydrolysis, a part of the glycolysis, may cause the pH to fall in the ischemic brain. The inventors observed that ischemia-related injury is probably not caused by acidification of the tissues or cells, but rather may be caused by the calcium flux into cells mediated by a member of the ASIC family, particularly ASICa. Selective inhibition of ASICa channel activity may thus reduce this harmful calcium flux, thereby reducing injury and brain cell loss. The overall mechanism of the ischemic process remains unclear, but the clinical studies performed in developing this treatment show promising results for mitigating brain damage.
This exciting innovation improves upon existing stroke therapies both by broadening the treatment window, and by incurring fewer side effects, a prospect which will appeal to all patients. When it comes to strokes, it is imperative that victims obtain treatment as quickly as possible, before they have suffered irreparable damage. This patent presents an intriguing solution to negating brain cell loss.