Researchers have discovered that a drug marketed to slow the progression of memory loss in Alzheimer's disease may also prevent brain damage in as many as 35 percent of premature infants.
Scientists at Children's Hospital Boston in a study published in The Journal of Neuroscience say they used memantine (brand name Namenda) to stop strokes—that would result in learning difficulties, behavioral problems and faulty motor function—in rats. The researchers hope to receive permission sometime in the next five years to test their new treatment in premature babies who suffer strokes.
Thanks to medical and technological strides, children as young as 23 weeks old (average pregnancy is about 40 weeks) are now able to survive, according to study co-author and neurologist Frances Jensen. But infants this young have less oxygen in their blood—because their lungs are not fully functional and their breathing is labored—leaving them prone to strokes (caused by a lack of oxygen to the brain).
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Preemies "are a very very fragile group of patients," Jensen says, adding that the strokes are the main cause of cerebral palsy—an incurable neurological disorder that affects the motor function of 500,000 people in the U.S., with 8,000 infants diagnosed yearly.
When nerve cells (neurons) do not get enough oxygen, they cannot make enough energy to function properly. As a result a neurotransmitter called glutamate, which revs up the cells to fire (send electrical signals between one another), builds up between brain cells. Normally, the neurons transport the glutamate across their membranes, thereby removing the prompt to fire. But without oxygen, their energy is depleted and they are powerless to remove it. Eventually, this buildup causes them to overactivate, leading to cell death and stroke.
Researchers found that memantine blocks a glutamate-sensing protein on a brain cell's surface so it will not activate even in the neurotransmitter's presence. In premature babies, this protein is only found on a type of brain cell called an oligodendrocyte, which makes a fatty coating that insulates the parts of nerve cells that transmit electrical signals to neighboring cells. Without the coating, called myelin, neuronal communication is disrupted, causing cognitive deficits and motion-related illnesses, as in cerebral palsy.
Jensen and her colleagues temporarily blocked blood flow to one side of the brain in rats to cut off the oxygen supply. (The other side of the brain was left alone so the researchers could directly evaluate the effect of their treatment.) The scientists then gave the injured animals four doses each of memantine over the next 48 hours.
The premature rats that received memantine were protected from a great amount of premature cell death that oxygen depravation should have caused. The animals that did not receive treatment, however, suffered from strokes. The injury also affected the development of the animals' cortices (the brain's central processing unit); untreated animals had smaller cortices on the stroke-damaged sides of their brains.
"We were able to protect against the injury and consequences of the injury," Jensen says. Researchers, she adds, plan to do more safety studies and, if all goes well, hope to test the drug at Children's Hospital on premature babies that suffer strokes.
Memantine costs around $120 to $150 per month for a prescription (without insurance), according to Martin Farlow, a neurologist at the Indiana University–Purdue University at Indianapolis School of Medicine. Potential side effects are generally mild and include dizziness, constipation, increased blood pressure and headache.
"It's certainly not a cure for anything [related to Alzheimer's]," says Farlow. "But, it has modest efficacy in patients with modest to severe Alzheimer's, improving cognitive functioning and functioning activities of daily living and behavior."