Pill Could Reverse Effects of a Stroke Long After It Hits
May 30th, 2012 by admin

(Technology Review) – For the 800,000 people in the United States who suffer a stroke each year, the window for drug therapy closes in the first few hours after the attack. That leaves some seven million stroke survivors in this country alone with no medical alternative beyond physical therapy. A small pharmaceutical company in New York hopes to change that with a drug that may help patients regain some of their lost mobility six months or more after a stroke.

Strokes happen when blood stops flowing to part of the brain, often due to a blood clot. Without blood to bring new oxygen, cells in the affected region start to die. If the symptoms of stroke are recognized quickly enough and the victim is brought to a hospital within a few hours, doctors can administer a clot-dissolving drug to minimize the damage. But only a small fraction of stroke patients seek medical attention soon enough for this intervention.

“If they miss this therapeutic window, the consequences are heavier, so it’s important to be able to do something for those patients who miss that window,” says Francesca Bosetti, a stroke expert with the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

In the future, stroke patients who miss this window and are affected by reduced mobility long after their stroke may be able to turn to a drug that helps damaged nerves transmit electrical signals in the brain.

Earlier this year, Acorda Therapeutics reported that the compound dalfampridine improved motor function in both the forelimbs and hind limbs of rats that had suffered a stroke. This month, the company began recruiting patients for a clinical trial to test the effects of the compound in human stroke patients. Acorda plans to enroll about 70 people who have had a stroke at least six months prior. “That’s the time that deficits seem to stabilize, so we can eliminate naturally occurring improvements in patients,” says Jeff MacDonald, an Acorda spokesman.

Acorda is focusing on neurological disorders at a time when many pharmaceutical companies seem to be turning away from such maladies. The company was founded in 1995 to treat spinal-cord injuries and has since taken on other neurological conditions, including multiple sclerosis and stroke. The company originally licensed dalfampridine from drugmaker Elan in the hope of using it to treat spinal-cord injuries, but instead it found more success in treating multiple sclerosis patients. “We followed it to where it was leading,” says Andrew Blight, chief scientific officer for Acorda.

Spinal-cord injuries still garner a lot of focus from the company, which hopes to begin testing acompound licensed from Medtronic that protects neurons from the wave of cell death that follows the initial injury. Medtronic had already shown the compound to be safe in healthy patients, and later this year, Acorda plans to test its efficacy in patients in the first hours after a spinal-cord injury.

Patients with injured spinal cords are not nearly as numerous as stroke patients, “but if you are talking about costs to society, spinal-cord injuries are extremely expensive,” says Naomi Kleitman, a spinal-cord injury expert with NINDS. “They tend to happen in fairly young people who need a lot of medical and assistive help if they have severe injuries.”

The company is also looking to treat longer-standing spinal-cord injuries with a drug that would help break down the scar tissue that forms around a spinal-cord injury. The scar tissue is thought to prevent nerves from establishing the new connections that may help patients recover some functionality. The product is still in early development, and one challenge will be devising a method to deliver the large scar-busting molecule to its target site.

Despite the pressing need, the small market for spinal-cord injury drugs may be one reason the condition doesn’t get a lot of attention from pharmaceutical giants. “No one else wants to develop compounds to treat spinal-cord injury as seriously as Acorda,” says Edward Hall, a neurologist and spinal-cord and brain-injury specialist at the University of Kentucky in Lexington. “These aren’t going to be billion-dollar-a-year products.”

Numbers will not be an issue for long-term stroke patients. Stroke is the leading cause of adult disability, and the number of people living with its effects is growing. “We are getting better at preventing stroke death, but the incidence is going up because the population is aging, and age is the greatest risk factor,” says S. Thomas Carmichael, a neurologist and neurorepair researcher at the University of California, Los Angeles.

Relatively few groups are working on treating the effects of a stroke more than six months after it occurred, says Carmichael, in part because the disorder is tricky to model in lab animals.

“It’s great for the field that [Acorda] is there,” he says. “Right now, there are no pharmaceutical options.”

However, Carmichael cautions that even six months or more after a stroke, patients can respond to focused rehabilitative intervention, which suggests that movement is an important part of recovery. “You have to pay attention to physical activity.” A patient’s own activity level can confound a trial if it’s not well monitored, but it could also lead to the greatest outcomes, he says, if made a part of it.