A Top Gun Takes Aim at Strokes
Dr. Jackson Streeter once held the ultimate cool job. In the mid-1990s he was the first medical doctor to be a pilot in the elite U.S. Navy Fighter Weapons School, more commonly known as TOPGUN—the same group immortalized by Tom Cruise in the 1986 movie. Streeter, now 46, had wanted to join ever since high school.
Nevertheless, he gave it all up in May, 1997, to start a company, Carlsbad (Calif.)-based PhotoThera, built around an unlikely laser therapy he learned about from an obscure Hungarian medical journal. Streeter has placed his hopes on an experimental device that, despite its high-tech underpinnings, looks a bit like a hair dryer. His goal is to crack one of medicine's toughest problems: protecting the brain during a stroke.
Streeter was trained as a surgeon at the University of Nevada School of Medicine on a Navy scholarship and knew so little about business when he struck out on his own that he had to buy a book on how to write a business plan. He decided to trade in Right Stuff-style glamour for the life of a struggling entrepreneur because he believes he may have a real breakthrough in a field where pharma companies large and small have produced only failures. His device, called NeuroThera, is still in clinical trials, but it is gaining respect from stroke specialists and once-skeptical venture capitalists. And nearly everyone gives Streeter credit for thinking about this devastating disease in a new way.
Strokes, often called brain attacks, are the second leading cause of death worldwide. Each year some 750,000 Americans fall victim to stroke, caused either by an artery blockage or intercranial bleeding, and 160,000 of them die. Fifty percent of survivors are left with such impairments as speech loss or paralysis. Consequently, stroke is the leading cause of long-term disability, costing the U.S. $63 billion each year.
A DECADE OF FAILURES
Despite this huge disease burden, there is only one stroke drug available, Genentech's tPA, approved in 1987. TPA is effective, however, only if given within three hours of the event; just 5% of stroke victims make it to the hospital in time.
More than 1,000 other stroke drugs have been tested over the past decade, and not one has worked. The most eagerly anticipated was NXY-059, jointly developed by AstraZeneca and Renovis. But after promising early results, researchers reported in October, 2006, that the drug failed utterly in a 3,200-patient clinical trial. "This is a very frustrating field," says Dr. Gregory W. Albers, director of Stanford University's Stroke Center. "The brain is just so extremely complex."
There are two types of stroke. About 85% are ischemic, caused by a blood clot or plaque fragment that blocks an artery to the brain, depriving neurons of oxygen and nutrients. The remainder are hemorrhagic strokes that occur when a blood vessel leaks into the brain. It can take emergency room doctors an hour or more to figure out which type of stroke it is before they can administer tPA, which works only for ischemic strokes. All the while, 2 million brain cells are dying every minute that the brain is deprived of oxygen.
The Food & Drug Administration did approve one device for stroke in 2004, the Merci Retriever. Made by Concentric Medical, it is a tiny wire with a corkscrew-like tip that a surgeon uses to skewer the clot and pull it out. But enthusiasm for the Merci device is lacking because it is difficult to use and was tested without a control group. Concentric is expected to report on a follow-up trial of the Merci Retriever early next year.
There are other treatments in trials, none of them ideal. Inducing hypothermia protects the brain, for example, but lowering patients' temperatures can be difficult and painful. Doctors are also experimenting with an antibiotic that may reduce brain inflammation. And Royal Philips Electronics just announced it will explore the use of ultrasound to break up stroke-causing clots.
Streeter wasn't looking to enter this clinical morass back in the Navy. Instead, he was seeking treatments for neck injuries that fighter pilots often suffer in the cockpit. He came across some obscure reports by Andre Mester in Budapest and Tiina Karu in Moscow, on experiments using low-level laser beams to heal soft-tissue injuries. The more he researched this unusual treatment, the more he thought it might be able to protect brain cells threatened by stroke. "I left the Navy, my home for 12 years in 1997 and filed papers to start my company the next day. I didn't have a clue how hard it would be," he says.
Streeter, more low-key scientist than brash entrepreneur, proceeded to sink all of his savings into PhotoThera. He borrowed more money from family members and took out a bridge loan to keep the company going. He quickly learned that venture capitalists did not have a lot of interest in stroke, given all the prior failures. There was even less enthusiasm for funding a treatment that sounded like a New Age gimmick. "Everyone was interested until I asked them for money," he says.
The device that Streeter developed is definitely exotic. NeuroThera uses a ray of near-infrared light to stimulate tiny cellular structures called mitochondria, which provide energy in each living cell. The mitochondria residing in neurons shut down during a stroke, leading to the death of brain cells. Streeter discovered that in animals, a near-infrared beam directed at the skull is absorbed by the mitochondria and kick-starts them into producing energy again.
His idea would need a lot of testing to convince the FDA and jaded neurologists, however. "We are certainly intrigued by the laser approach, but the fact is we really don't understand how it works," warns Dr. Helmi Lutsep, associate director of Oregon Health & Sciences University's Stroke Center. "Lots of approaches don't hold up under testing."
SUCCESSFUL FIRST TRIAL
Still, Streeter managed to drum up $750,000 in financing from Hamilton BioVentures and California Technology Ventures in 2001, in part by crashing a Goldman Sachs investment meeting in San Diego. Positive data in animals helped him raise an additional $4.35 million, then $19 million more, and finally in 2006, $30.5 million. The money enabled PhotoThera to put together a 120-patient randomized trial in Europe and Israel last year.
The trial went well. The researchers reported in the June issue of Stroke that 70% of patients who received the two-hour laser treatment had a good outcome, compared with 51% of the control group. Plus, the therapy could be delivered up to 24 hours after a stroke.
With those results in hand, Streeter persuaded the FDA to approve a U.S.-based trial of 660 patients that started last January and will run until spring of 2008. He still has to convince the medical community that his approach has merit. Dr. Scott E. Kasner of the Hospital at the University of Pennsylvania says he started laughing when he read PhotoThera's clinical trial proposal. "The idea sounded just too crazy. But the more I thought about it," he says, "I realized it made a kind of sense." He signed on as an independent investigator.
Many more stroke doctors are desperate enough to experiment with almost anything that could make a difference. "It's so novel I'm not sure what to make of the theory behind it," says Dr. Eric E. Smith, associate director of Massachusetts General Hospital's stroke unit. "But there is promising human data. If it makes people better, I'm all for it."
A research firm is pessimistic about new drugs to treat stroke
Decision R esources, a research firm specializing in health care, concludes in a July report that the acute ischemic stroke market is a "graveyard for drug development." It doesn't expect any new drug therapies for stroke between now and 2016. Innovative drug/device combinations are the best near-term hope.
The most heartbreaking stroke patients are surely children—3 out of every 100,000 suffer such events. A Toronto-based study in the Nov. 5 issue of Pediatrics says there are warning signs: Toddlers with strokes were 10 times more likely to have iron-deficiency anemia than other children their age, and kids with this condition accounted for more than half of all strokes in children.
Arnst is a senior writer for BusinessWeek in New York