THURSDAY, June 13, 2002 (HealthDayNews) -- An experimental protein that acts as a bypass appears to bring relief to patients whose leg arteries are blocked by the buildup of hard plaques.
Treatment with the drug, recombinant fibroblast growth factor-2 (rFGF-2), led to small but significant gains in walking times in people with moderately advanced symptoms of exercise-induced claudication. The condition is caused by obstructed arteries in the lower body.
The protein triggered the legs to sprout a network of small veins -- a process called angiogenesis -- to reroute blood around blockages and eased the stress on nutrient-taxed muscles.
Claudication affects an estimated 15 percent of people over age 55, causing severe, sometimes crippling pain and cramping during movement and exercise. Like angina in the chest, the discomfort results from narrowing of arteries in the legs, generally in the calves.
When these arteries become blocked, they can't get enough oxygen to handle lactic acid and other chemicals produced during walking or running. In some cases, the obstruction is so severe it requires amputation of the lower leg.
Enter angiogenesis. The theory behind this therapy is to spur the formation of mini vessels that bypass narrowed arteries and restore proper blood flow to the legs. Doing so should at least partly relieve the symptoms of claudication.
And the latest research, which appears this week in The Lancet, suggests the approach seems to work.
The researchers tested rFGF-2 in 174 men and women, whose average age was in the mid-60s and who all had intermittent claudication. One third got a single infusion of the drug and then a dose of dummy substance, or placebo, 30 days later; another third got two doses of the drug at day one and day 30; and the rest received one infusion of a placebo solution.
After 90 days, the group that got the single dose could walk almost two minutes longer on a treadmill test than they could at the start of the trial. Those who received two doses had more modest gains, and the placebo group showed a slight improvement -- a not uncommon phenomenon in vessel studies, experts say.
Dr. Brian Annex, a Duke University vessel expert and a co-author of the study, says it's not clear why two doses weren't more effective than one. An explanation, he says, is that the drug acts like a light switch -- it either sets off a cascade of vessel growth or it doesn't.
The new study is a turn-around of sorts for rFGF-2, Annex says. The drug failed to help patients with coronary artery blockages in an earlier trial published this year. The difference may have something to do with the nature of muscles in the legs and the heart, or the way the compound was administered, he says.
Dr. Stan Rockson, a Stanford University vessel specialist familiar with the latest work, says the new results are promising.
Even though the absolute level of improvement in the trial was modest, claudication doesn't spontaneously resolve if untreated.
"The fact that the group that got it improved in terms of functional capacity would make [the drug] a significant benefit," says Rockson. "It certainly rivals the best we can do with any other therapy."
Standard treatments currently include bypass grafts and exercise.
Rockson says it's possible the drug will be even more effective once scientists work out the correct dosage.
The protein appears to be relatively safe, Annex says. Side effects in the most recent study included a few cases of excess protein in urine -- a sign of potential kidney trouble -- and low blood pressure immediately after the infusions.
Experts have worried that promoting new vessels might encourage the growth of dormant tumors, Rockson says. But the researchers found no evidence of an increased risk of cancer in the patients who took the protein.
Chiron Corp., an Emeryville, Calif., biotech company that makes rFGF-2, sponsored the study and is planning a follow-up trial for the fall.
What To Do
For more on claudication, try Heart Canada. To find out more about angiogenesis as therapy, check the Angiogenesis Foundation.
