In the study, Inosine was shown to stimulate nerve cells in undamaged parts of the brain to grow new connections into brain areas that had lost their normal connections as a result of a stroke; this "rewiring" partially compensated for the loss of the original connections, and resulted in significant improvement in several types of behavior compared to rats that did not receive Inosine.
"These findings are of both scientific and clinical interest," said Larry Benowitz, the Principal Investigator on the study. Dr. Benowitz is the head of the laboratory at Children's Hospital where much of the work was carried out, and an Associate Professor of Neurology at Harvard Medical School. "The study shows that Inosine induces a great deal of rewiring in the brain after stroke. This rewiring is apparently sufficient to promote substantial functional recovery. In terms of clinical implications, Inosine, which appears to have no apparent side effects in animals thus far, has potential as a novel nerve regeneration approach to treatment of stroke and other types of brain injuries."
It is estimated that 750,000 people suffer first or recurrent strokes every year in the U.S. Stroke occurs when the brain is deprived of its blood supply either by a blood clot blocking a blood vessel (ischemic stroke) or a blood vessel rupturing in the brain, leaking blood and damaging tissue (hemorrhagic stroke). The third leading cause of death in the U.S. after heart disease and cancer, stroke claims the lives of 160,000 Americans each year and costs $30 billion in medical and rehabilitation expenses and lost productivity. More than half a million Americans survive stroke each year, often with drastic losses that impact their quality of life and basic functioning. Current treatments after stroke are limited to methods to restore blood flow and prevent the damage from spreading; as yet, there are no clinically approved methods, however, to enhance wiring.
Boston Life Sciences, Inc (BLSI) is developing Inosine for the treatment of stroke and other CNS injuries. Marc Lanser, M.D., Chief Scientific Officer of BLSI stated "We are excited to be associated with this extremely important study of Inosine, which has the potential to be the first nerve regeneration approach to treatment of stroke. In a separate study (not included in this publication) we have found that Inosine is effective even when administered as much as 24 hours after stroke. This is an additional important potential advantage over other current therapies."
Inosine dramatically improved performance on each measure used for this animal study:
- When held by the torso and lowered toward a table, rats treated with Inosine after a stroke showed greater ability to place their paws on the table than untreated rats. After 19 days, treated rats had nearly normal paw-placing ability, whereas untreated rats remained 50% below normal.
- In a separate experiment, animals were trained to reach through the bars of a cage to grasp food pellets placed just outside. By the 4th week of the study, with their unaffected paw restrained, half of the Inosine-treated rats used their stroke-affected paws to reach for food, compared to none of the untreated rats with strokes. Moreover, when Inosine-treated rats were allowed to reach with either paw, 20% continued to use the paw affected by stroke. In comparison, very few untreated rats attempted to reach for food using the affected paw. Of those who did try, none succeeded in getting food and all attempts eventually stopped.
- Treatment with Inosine also helped improve rats' swimming function after a stroke. Normally, rats unaffected by stroke swim using only their hind limbs, holding their forelimbs motionless under the chin. After a stroke, rats were no longer able to hold their forelimbs motionless. However, by week 8, those that received Inosine showed significantly greater ability to regain control of their forelimbs while swimming.
Results of anatomical studies correlated with functional results. Typically, after a stroke on one side of the brain, nerve cells in unaffected areas, including those on the undamaged side of the brain, show a small amount of compensatory growth. Inosine increases the capacity of nerve cells to make new connections to those brain areas that have lost their normal inputs because of a stroke. The Inosine-stimulated increases were 3 to 4 times higher than in the rats that did not receive Inosine after stroke.
"Stroke has been a poorly understood and inadequately treated area of medicine," said Dr. Lanser. "These data offer great hope that we may finally see a breakthrough in treatment that can repair the damage wreaked by stroke."
About Boston Life Sciences, Inc.
Boston Life Sciences, Inc. is a biotechnology company developing novel diagnostics and therapeutics for Parkinson's Disease (PD) and Attention Deficit Hyperactivity Disorder (ADHD) as well as treatments for cancer, autoimmune disease, and central nervous system disorders. BLSI's products in development include: Altropane, a radio imaging agent for the diagnosis of PD and ADHD; Troponin I, a naturally-occurring anti-angiogenesis factor for the treatment of solid tumors; AF-1 and Inosine, nerve growth factors for the treatment of stroke, spinal cord and optic nerve injury; novel therapeutics for the treatment of PD and ADHD; and transcription factors that may control the expression of molecules associated with autoimmune disease and allergies. Since 1992, BLSI has raised more than $65 million to fund its research programs, which are primarily conducted at Harvard Medical School and its affiliated medical centers.
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