Photo by: patricia pierce via Flickr
The hibernation of squirrels was the inspiration behind a drug that scientists at the National Institute of Neurological Disorders and Stroke are developing.The medication hopes to trigger the same cellular changes that hibernating squirrels go through that could prevent brain damage.
During the hibernation process of the tree-climbing animal, a protective process happens in their cells that allows the squirrel's brain to function with reduced blood flow and oxygen.After the animal awakens, the squirrel does not suffer any ill effects even if it was deprived of essential nutrients, The Telegraph reported.
Ischemic Stroke in Humans
When an ischemic stroke happens, the blood supply – which contains sugar and oxygen – is cut off to the brain.Cells die and it often results in paralysis and speech problems.Joshua Bernsock, a graduate student at NINDS, said the aim of the drug is to turn on the process hibernators that appear to use to protect the brains, it would help protect it during a stroke and ultimately help people recover.
The cellular process, called SUMOylation, goes into overdrive when squirrels hibernate and it protects the animal's cells.Ebselen, an enzyme, boosted the process, the scientists discovered.The injection of ebselen into the brain cells of the animal resulted in the squirrel staying alive, even if it was deprived of oxygen and blood.
The enzyme, when injected into healthy mice in further experiments, also increased the SUMOylation of the rodents' brains. When an enzyme attaches a Small Ubiquitin-like Modifier, a molecular tag, to a protein, it alters the activity and location in the cell.
There are other enzymes, SUMO-specific proteases, which can detach the tags, decreasing SUMOylation.The researchers from NINDS partnered with scientists from the National Center for Advancing Translational Sciences of NIH to study if any of more than 4,000 molecules from the NCATS small molecule collections could improve SUMOylation by blocking an SENP, the SENP2, which, theoretically, protect cells from a shortage of life-sustaining substances.
They first used an automated process to study if the compounds stopped the SENP2 from cutting the connection between a small metal bead and an artificial SUMO protein created in the laboratory of Wei Yang, an associate professor at Duke University in Durham, North Carolina.
Along with computer modeling and more tests done in and outside of cells, it whittled the thousands of candidate molecules to eight that could bind to SENP2 in cells and were non-toxic.In mice cells, ebselen and 60-thioguanine were found to boost SUMOylation in rat cells and keep the rodents alive even if there were no blood and oxygen.
Ebselen boosted SUMOylation in the brains of the healthy mice in the final experiment than in a control injection.The researchers did not use 6-thioguanine because it is a chemotherapy medication with side effects which makes it unsuitable as a potential stroke treatment.The scientists are now planning to test if ebselen can protect the brains of animal stroke models.
According to Bernsock, the approach of the team could inspire similar attempts to treat neurological conditions by targeting pathways with wide-ranging effects because SUMOylation affects a variety of molecules.
Experts believe that in humans, if a treatment can be quickly administered to stroke patients, it could help the brain survive without blood and oxygen and the outcome for patients can be radically improved.The only method, so far, to minimize death induced by stroke is to remove the clot as soon as possible.
The general rule is to seek care for ischemic stroke patients within six hours to avert the risk of permanent disability.But a new study, published in the New England Journal of Medicine, said the window can be as long as 24 hours for some stroke patients, Sentinel Source reported.
The discovery could end the decades-long search by scientists for an effective brain-protecting stroke therapy but none came up until the squirrel.Dr.Francesca Bosetti, the program director at NINDS, said that if the compound that the research identified successfully cuts tissue death and improves the recovery in further experiments, it can lead to new approaches for the preservation of brain cells in the aftermath of an ischemic stroke.
Bernsock said he hopes the study, published in The FASEB Journal, would encourage other scientists to look to nature to solve medical problems that are pressing.He prefers to work on projects with a clear relevance to patients and outcomes that can lend itself to new therapeutics for people in need.
In Britain, around 100,000 people suffer from strokes each year, of which 85 percent are ischemic strokes.Among the survivors, two-thirds will leave with a disability, adding to the 1.2 million people in the UK living with the after-effects from a stroke.
Medical.net placed the number of stroke incidents in the US at 800,000 a year, with 87 percent ischemic strokes.