Newswise — A Henry Ford Hospital researcher has been awarded the first National Institutes of Health (NIH) grant aimed at developing therapies to "remodel brains" injured from stroke and other brain traumas.
The $6.5 million, five year Program Project grant, awarded to Michael Chopp, Ph.D., scientific director of the Neuroscience Institute at Henry Ford Hospital, is for further development of cellular and drug therapies that restructure the brain to help people recover from traumas such as stroke or head injuries.
The multifaceted study will primarily focus on the treatment of stroke and traumatic brain injury with cells derived from the adult bone marrow. These cells essentially restore neurological function after stroke and brain injury. The mechanisms responsible for this highly effective therapy will be investigated.
In addition, resources from the grant will be used to develop and implement new forms of cell and drug therapies to restore neurological function after stroke and brain trauma.
Dr. Chopp is one of a handful of researchers in the country currently working on an area known as brain remodeling. He develops and tests different cell-based therapies as well as compounds that may generate new brain cells in animals and improve function after neural injury and stroke.
In addition, neurologists at Henry Ford Hospital using data generated by Dr. Chopp and colleagues are expected to launch human studies soon using pharmaceutical agents (sildenafil-Viagra and statins) to help stroke victims. Patients identified with ischemic stroke will be eligible for these research trials.
"The laboratory studies strongly suggest that we will someday successfully treat patients days or even weeks, after they have suffered a stroke," said Dr. Chopp.
Each year about 750,000 people experience a new or recurrent stroke attack and it is the nation's third leading cause of death, ranking behind diseases of the heart and all forms of cancer.
Currently, tissue plasminogen activator (t-PA) is the only treatment for ischemic stroke " the cause of more than 80 percent of all strokes " approved by the U.S. Food and Drug Administration.
But the clot-dissolving drug must be administered within three hours of initial stroke symptoms for effectiveness. In addition, t-PA treatment reaches only 1 to 2 percent of Americans.
Among the reasons for the low use rate are that while the general public is familiar with the warning signs of a heart attack, one-third cannot name one warning sign of stroke; the average time that elapses before a stroke patient goes to a hospital after experiencing initial symptoms for a stroke is 12 hours and a shortage of hospitals with the comprehensive resources to rapidly assess and treat stoke victims.
Dr. Chopp has focused on the development of therapies to restore function after neuro-injury and neuro-degenerative disease.
His team has used cellular and pharmacological therapies with laboratory animal models (rodents) to successfully treat stroke, head trauma, Parkinson's disease, multiple sclerosis and spinal cord injury, and is developing therapies for other neurological diseases such as brain cancer.
These cellular and/or pharmacological therapies do not resurrect injured or dead brain tissue but instigate growth of new brain cells, new blood vessels, and new electrical connections in tissue near the site of injury or disease. In this way, these therapies work to remodel the brain or spinal cord to take on the functions that have been lost by the injured or dead tissue.
"Think of the brain as a house," says Dr. Chopp. "If a tree falls on your house, what you want most is to fix the damage to restore your daily quality of life. Remodeling the brain, like remodeling a house, may require new plumbing, such as new blood vessels; new electrical connections or new synapses; and new rooms or new brain cells in order to regain function."
In prior research:
"¢ Dr. Chopp and his research team have demonstrated that compounds, like Viagra and statins, create new brain cells which are created in both elderly as well as young animal subjects. When animals with stroke are treated with Viagra or a statin, the drug provides a very significant neurological functional benefit. These drugs stimulate brain "plasticity." The animals do much better on many different outcome measures, including motor function, neurological outcome and weight gain. In addition, there are far fewer functional deficits.
"One can be treated with Viagra or statins days after stroke and there is a significant reduction in neurological deficit and a significant induction of new brain cells," said Dr. Chopp. Similar studies and successful restoration of neurological function after stroke and trauma have been performed by Dr. Chopp and colleagues.
"¢ Human umbilical cord blood cells may become a new source for treatment of stroke. In one study, rats injected with umbilical cord blood cells 24 hours after the onset of stroke showed dramatic improvement in recovery two to three weeks later. For example, rats that lost motor skills from the stroke were later able to run on a treadmill as a result of this treatment. "Stem cells collected from umbilical cord blood are able to travel to the stroke-damaged area of the brain and act as a source to help restore the function lost by brain cells that died or were injured by the stroke," said Dr. Chopp.
The rat model of stroke is considered ideal for experimental research as the effects of stroke in people are similar to those seen in rats. These laboratory research findings indicate the need to pursue the development of new clinical trials for people with stroke, according to Dr. Chopp. Cord blood cells have a potentially wider window of opportunity to help people with stroke compared to the current use of t-PA.
"¢ Dr. Chopp and his team used " for the first time " bone marrow cells to reduce stroke-induced disability. The study found that intravenous treatment with adult donor rat, mouse or human stromal cells (mature cells from bone marrow) allowed the rats to return to normal or near normal function within 14 days of a stroke.
"This study suggests that an infusion of the stromal cells provides significant benefit to the stroke patient and is easily administered," he said. "We believe we have a therapy that shows promise in treating stroke, Parkinson's disease, spinal cord injury and traumatic brain injury."
The approach involves removing stromal cells, growing them in culture, and then infusing them back into the animal where they migrate to the site of injury " in this case the brain. These cells are not rejected by the rat. The animals were given neurological, motor skill and sensory function tests before the stroke, at day one, one week and up to four months after the stroke. In general, the animals treated with infusion of stromal cells scored significantly better on the tests and neurological function was essentially restored.
The stromal cells are smart: when taken out of their natural environment within bone and moved to a new neighborhood via injection into the bloodstream, they know how to travel and where to go and can find their own way into brain or spinal cord near the target site of injury or disease. Once there, these cells become like major production factories, spewing out an array of factors that activate the brain or spinal cord to produce new cells (neurogenesis), new blood vessels (angiogenesis), and new electrical connections (synaptogenesis).
In addition, these cells help to stop the process of cell suicide (apoptosis). After an injury to the brain or spinal cord, in the tissue that surrounds the site of injury there are some cells that automatically begin to self-destruct. "We have discovered that the marrow stromal cells produce factors that inhibit this cell suicide process. Together, all these factors that stop healthy cell suicide and that create new cells, new synaptic connections and new blood vessels each work in combination to become integrated into the brain or spinal cord to restore function that has been lost by the aging, injured or diseased tissue," said Dr. Chopp. Similar studies in Dr. Chopp`s laboratory using cells harvested from the lining of the cerebral ventricles have demonstrated substantial benefit in ameliorating neurological deficits after stroke.
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