EUGENE DOCTOR INVENTS TOOL TO FIGHT STROKE.

Byline: Tim Christie The Register-Guard

There is a maxim among doctors who treat strokes by threading catheters through arteries leading to the brain: Time equals brain.

"The quicker you can intervene, remove the clot, restore blood flow, the more brain tissue is going to be viable, and the better the patient is going to do," says Dr. J.P. Wensel, a Eugene neuro-radiologist.

It was that maxim that gave Wensel the idea nine years ago for a new way of treating strokes, by using a mechanical device to quickly extract a clot instead of trying to dissolve it with drugs.

That idea bore fruit last week when the U.S. Food and Drug Administration approved the Merci Retriever, the first device to use mechanical means to rid the brain of potentially debilitating and deadly blood clots.

The Merci Retriever, developed by a privately held California company called Concentric Medical, works and looks like a tiny, high-tech corkscrew, but Wensel prefers another term.

"It's actually not a corkscrew," he said. "I hate that term. It's a helix of diminishing radius."

Usual treatment may not work

Strokes afflict about 700,000 people annually in the United States. Of those, about 83 percent are ischemic strokes, in which a blood vessel in the brain is blocked by a blood clot.

Strokes killed 163,538 people in 2001 and is the leading cause of serious long-term disability in the United States, as well as the third-leading cause of death.

Concentric Medical's first test of the device indicates it can play a role in treating people who would otherwise die or be disabled.

"It saved people's lives," Wensel said. "That's a huge personal reward to be a part of something like that."

The FDA approved Merci Retriever - Merci is an acronym for Mechanical Embolus Removal in Ischemia - after it was tested on 141 patients at 25 medical centers around the United States.

The device was used on patients who were ineligible for the standard treatment, in which doctors infuse the clot with the drug tPA, for tissue plasminogen activator.

The drug works like Drano to dissolve clots but if it's used more than three hours after a stroke occurs, its effectiveness diminishes and it can actually increase the chances of cranial bleeding.

Up to 8 hours after stroke

The Merci Retriever, made from a titanium-and-nickel alloy called Nitinol, can be used up to eight hours after a stroke. Of the 141 patients who were treated with the device, 52 percent had their blood flow restored, said Gary Curtis, Concentric Medical's chief executive officer.

The company's study of the drug was narrowly designed and intended to measure whether the device restored blood flow to the brain, not whether it made patients better.

A FDA advisory panel reviewed the device in February, when 114 patients had been treated. The panel of experts examined not only cases in which the device restored blood flow, but also those in which something went wrong - known as " "serious adverse events."

The agency found a total rate of serious adverse events of 12 percent, according to minutes of the advisory panel's meeting.

Device- and procedure-related adverse events occurred in eight of 114 patients, or 7 percent. Four patients experienced serious device-related adverse events - two had strokes in other parts of the brain, and blood vessels were torn or perforated in two others.

Forty-five patients died after 90 days, two suffered new strokes and two suffered heart attacks.

Another problem involved the device itself. Seven of the 265 devices fractured; of those, six device tips detached in patients, two of which were retrieved.

Almost 10 percent of devices had some type of failure, which appeared to be related to doctors overtorquing the device, FDA officials said.

The panel concluded in February that it didn't have enough information to show that the Merci Retriever was safe. Members said a randomized, controlled trial was needed to demonstrate its benefits. Such a trial, funded by the National Institutes of Health, is now under way at UCLA.

Curtis, the Concentric Medical CEO, said FDA staff members told the company it needed to respond to the panel's questions. So, after it completed its analysis of all 141 patients, it addressed the panel's questions and the FDA approved the device.

Potential for big results

In the short term, the device will remain in the hands of highly trained doctors who know how to put catheters into the blood vessels of the brain, Curtis said.

The device was tested at Oregon Health & Science University and Providence St. Vincent Medical Center, both in Portland. Dr. Wayne Clark, director of the Oregon Stroke Center at the OHSU School of Medicine, said the Merci Retriever "appears fairly safe" and has the potential to make dramatic differences in stroke therapy. But it needs more scientific scrutiny, he said.

"So far it seems to be working well and it seems to be safe," he said. "But we have not had enough patients that we can say it's any better than other treatments."

The Oregon Stroke Center is testing another device that delivers tPA and ultrasound waves simultaneously to break up clots in the brain.

From sketch to development

Wensel, an Iowa native, said he knew as soon as he came up with the idea that a tiny corkscrew could be an effective treatment for stroke.

"You can look at the device and say it's complex because of the materials it's composed of and the dimensions, but actually it's a pretty simple idea," he said.

Wensel earned his medical degree and a Ph.D. at the University of Iowa Medical School, then trained in Wisconsin, Arizona and Oregon before getting a fellowship in neuro-radiology at UCLA. It was there that he came up with his idea after becoming frustrated when some patients didn't respond to the standard treatment for stroke.

"I saw a couple patients (clot dissolving) didn't work on," he said, including one who died.

Wensel went home and made a sketch of a mechanical device he thought might do the job. He came up with the helix shape thinking it could wind its way into a clot so it could be extracted, he said.

He took the sketch to professor Pierre Gobin, who immediately embraced the idea, and the two men began working to refine it.

Wensel and Gobin took their idea to the UCLA intellectual property office, which applied for a patent. With a patent in hand, the co-inventors struck a deal with a subsidiary of Medtronics, one of the leading medical device makers in the world.

Medtronics began to develop the retriever device - originally dubbed the Clot Capture Coil - but went out of business, leaving Wensel and Gobin in limbo. They bought the patent back from UCLA and looked for another company to develop the device.

Company wins FDA approval

Concentric Medical, a privately held firm in Mountain View, Calif., that is backed by venture capital, was formed to develop the device in 1999. In exchange for their idea, Wensel and Gobin were given equity in the company.

Wensel stayed in touch with company executives but played no further role in its development or in the FDA approval process.

The doctor-inventor doesn't fit the image of a scholarly physician in a white lab coat. His crew-cut gray hair and burly build make him look more like a nightclub bouncer than a doctor, although his background as a heavyweight boxer in college and a martial arts instructor would qualify him for such a job.

About two weeks ago, company executives told him FDA approval was imminent. Last Monday, the company announced that the device had won FDA approval and Wensel breathed a sigh of relief.

"I'm not sure I clicked my heels but I think I probably jumped around a little bit," he said.

Solo practice in the future

After practicing radiology in Newport Beach, Calif., Wensel came to Eugene to practice radiology five years ago. Radiologists interpret medical images, such as X-rays, MRIs and CT scans, and do some interven- tions.

He recently left Radiology Associates and is taking some time off before he begins a solo practice.

He's working on other ideas for medical devices, with one patent pending and two others in preliminary stages, but he won't go into specifics. He said he's not ready to give up practicing medicine, however.

"I get some gratification out of solving problems in this way," he said. "Taking care of patients is obviously something I enjoy, but when we're talking about inventing something, the potential is there to help a large number of patients with one idea, which is also intriguing."