Spinal injury patients, advocates call FDA to approve stem cell trials

The story starts with three people.

. Logan Square resident Linda Cassady, 40, is a graphic designer, illustrator, business-owner, homeowner, pet-owner and, since a 1999 car crash, paraplegic.

"Ironically enough, [I was] T-boned by a paraplegic," she said, laughing.

The accident, in which the other driver broadsided her, cut off blood flow to her spine. She has sensation and can move her legs and feet slightly. She jokingly described her condition as having "to sit down for all of time" and her motion as "more like cocktail party amusement than it is useful."

"It's not that big of a deal to me that I got into the accident. I've got bigger problems than not walking, like paying my bills," Cassady said, adding "getting a boyfriend" to the list.

She said she would be willing to be part of the first round of human clinical trials using embryonic stem cells to attempt to repair spinal cord injuries ("Why not?" she said.), but wouldn't go to much trouble to pursue it. The clinical trials, which one California-based company hopes to start as soon as this summer, are just one of the slew of embryonic-stem-cell-based trials biotech companies are pushing the Food and Drug Administration to let them start this year.

. Bob Spielman, 59, of Arlington Heights, spends 2 ½ hours every morning doing a "bowel program" as he has no control over defecation.

He hasn't seen the second floor of his house in 17 years. Except for constant pain, he has no sensation below his chest ("You could stick a knife in my leg and I wouldn't feel it.")

He and his wife will celebrate their 37th anniversary in July.

"My situation is not as bad as others'," he said.

In 1991, a viral infection attacked his spinal cord and his immune system couldn't fight it. His cord is there, but useless. The virus ate the insulating myelin that helps transmit messages to his cord. Transverse myelitis is the name of his condition. A former vice president of a software company, Spielman returned to work for three months until the company's CEO warned him of an impending merger, advising him to go on disability.

Spielman wouldn't join the clinical trials.

"That's a tough question," Spielman said. "I guess I certainly wouldn't be the first person to try one, no. I wouldn't do it because of the unknowns. Could things become worse, for example? Could I end up with even worse pain or a different pain than I have now?"

Despite this, he fully supports stem cell research.

"I'm not looking at it from the point of view of helping me," he said. "I'm looking at it from the point of view of helping the next person who gets into a car accident or even the next person who has transverse myelitis or the next person who dives into an empty swimming pool."

. Michelle Lee, 25, of Glenview, spent three of the past four years traveling China seeking an acupuncture-based cure for her paralysis.

"I'm willing to try anything, pretty much," she said.

In a car crash five years ago, her vertebrae shattered and splintered into her spinal cord. She has no use of her legs and fingers. She has only slight motion in her arms. A corporate treasury analyst in downtown Chicago, Lee dictates into a voice recognition program at work. She cannot feel someone touching her, unless they squeeze deeply.

Lee is in this story because of a miscommunication. She didn't know the phone number she was given was for a reporter. She thought it might be for a recruiter for the trials she wants very much to join.

"If I were the guinea pig, that would be fine," Lee said after the confusion was cleared up. "It's not like I could get any worse, I guess."

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Three stories, three people and one hope - that stem cell therapy for humans will prove as promising as tests in lab animals and press reports suggest.

Stem cell research, particularly embryonic stem cell research, has gotten a great deal of attention in the popular media, from the New York Times to "South Park" and "Family Guy." It's a great story, with compelling characters (Lee, Cassady and Spielman), great conflict (are the four-to-five-day-old embryos from which the cells are harvested people?) and nifty sound bites (stay tuned). But the story is poised to become much more than just a story.

An FDA advisory committee met in April to discuss human tests of therapies based on stem cell research. Representatives of three biotech companies spoke at the meeting about their respective research. Advanced Cell Technologies is developing a therapy using embryonic stem cells to try to stop retinal degeneration that can lead to partial or total blindness. Novocell wants to treat diabetes. Of greatest interest to Cassady, Spielman and Lee, the company Geron wants to use embryonic stem cells to try to repair spinal cord injuries.

Representatives of all the companies said at the meeting they are ready to start human tests as soon as this year, but the FDA is making no promises that the conference will lead to anything.

The purpose of the conference, FDA spokeswoman Pepper Long said, was just to get the agency up to date on the most recent research.

"The science is at a point where it's important for us to get more information on this," she said.

Long said she could not confirm if any company had already submitted the needed paperwork to start human tests.

Jonathan Dinsmore, senior vice president-regulatory and clinical of Advanced Cell Technologies, said his company is getting the paperwork ready.

"We feel we've completed the kind of animal testing that is required and we're preparing that information for the FDA," Dinsmore said.

Rumblings and rumors, however, say at least one company already has submitted.

In an article previewing the conference, CNNMoney.com quoted analysts who said they believe Geron had already filed paperwork on its spinal cord injury therapy with the FDA. However, representatives of the Menlo Park, Calif., company would not confirm.

"The only thing we have disclosed is that we expect to initiate a clinical trial program this summer," Geron spokesman David Schull said. "Stay tuned."

What's right?

Part of the reason Linda Cassady would not pursue joining a clinical trial that she hopes could make her walk again is because she has bills to pay.

"I don't have the luxury of a lot of time," Cassady said. "I didn't get a big settlement [from the car crash]. I'm not wealthy."

It's exactly that connection between money and admittance into potentially helpful clinical trials that concerns bioethicist Laurie Zoloth, director of the Center for Bioethics, Science and Society at Northwestern University.

"If you have, say, 100 people who have devastating spinal cord injury, who do you take?" Zoloth asked.

Part of Zoloth's concern is that people might attempt to buy their way into trials - it has happened before. Another part is that some people might have the financial ability to join the trials, whereas others might not. This is the case in any trials for a new therapy, from drugs to radiations. Stem cells, she said, just prove particularly attractive.

"The theory of stem cells is that they would cure a disease by repairing the damaged cells, rather than treating the symptoms," she said.

Stem cell therapy has become lionized in the popular media, said Mercedes Rauen, executive director of the Spinal Cord Injury Association of Illinois [1]. The promise of a therapy that could cure, not treat, devastating injuries has become a powerful one.

"[There's] so much in the media, in the news media, that presents it as a cure is right around the corner and it's not," said Rauen, who wished it stressed that she does not have spinal cord injury.

Spielman, for example, remembers reading articles on the promise of stem cell research after he was injured in 1991.

The allure of stem cell research is great. The National Institutes of Health call stem cell research "one of the most fascinating areas of biology today."

Stem cells are cells that have the ability to become other cells. Critical in human development, the cells are vague templates of the various types of cells that make up the body. A stem cell could develop into the cells that make up the eye, as Advanced Cell Technologies hopes. Or the cells that allow the spinal cord to transmit messages from the brain, as Geron hopes.

Life begins with a sperm and an egg. It grows from there. In the first few stages of development, all cells are stem cells. One cell might grow and replicate into the cells that make up the nervous system. Others might grow and replicate into the cells that make up the limbic system. Or the heart. Or the eyes. Or the mole on the back of your neck.

There are many sources of stem cells. Blood from the umbilical cord cut from newborns has proved a promising field of research. Adults have stem cells, although the NIH notes that adult stem cells generally can only grow into cells of the type of tissue from which the stem cells were harvested. But the value of a stem cell is the variety of the cells it could become. For that, stem cells culled from undeveloped embryos have proved the most versatile.

There is no lack of interest in stem cell research, Rauen said. But this does not mean that all people who have, say, spinal cord injuries would be willing to put themselves on the line in the first round of clinical trials.

"Inquiries frequently come from someone new to spinal cord injuries, someone who was just injured," Rauen said. "Usually more from the families than the person injured."

Experiments have gone on for years in rats, mice and monkeys in the case of Advanced Cell Technologies' vision studies. The question is what to do with people.

A bit of history

One very boring-sounding phrase is "US policy regarding clinical trials."

The policy, however, was hewn only after a history of Nazi atrocities and a federal public health study in the South that went horribly awry.

The 1947 Nuremberg Code was designed as a means of judging Nazi doctors for gruesome and inhumane experiments conducted on Jews, Gypsies and homosexuals in concentration camps. The 1978 Belmont Report was commissioned in response to American experiments on prisoners, the mentally ill, disabled children and rural black men.

The last example comes from the Tuskegee experiment, in which 399 southern black men with syphilis -- at the time a fatal disease with no effective treatment options -- were told they were being treated for "bad blood." Instead, US Public Health Service researchers let the disease run unchecked to chart the disease's progression, autopsying the bodies after the men died. The experiment started in 1932 and was intended to last six months.

It lasted 40 years, long after penicillin, which cures syphilis, was discovered and widely used. The experiment stopped after health workers leaked the story to the Associated Press.

The Nuremberg Code and the Belmont Report are just two of the guiding documents the US government used to define a humane experiment. All the documents have one moral goal, Zoloth said; protecting the vulnerable.

"The Belmont report and other reports all have to do with poor people being used for research," she said, specifying that the reports protect the poor this in large part by requiring all participants be given full, informed consent before joining an experiment and have the ability to refuse to participate.

Then came AIDS.

In the early 1980s, rare and baffling diseases started appearing among homosexual men. Now known to be linked to what is now called acquired immune deficiency syndrome, the diseases were lumped together as GRID, gay-related immunodeficiency diseases. This was the technical term, as compared to the more colloquial "gay pneumonia" or "gay cancer."

No one knew how the disease was spread, nor how it started appearing among heterosexuals. It was mysterious, deadly and terrifying. When researchers began testing possible AIDS cures or drugs to combat the symptoms, people lined up to join the trials.

"Who gets the first chance, the first crack at a new research that could be very powerful." Zoloth said.

An incurable disease that at the time was considered a death sentence, AIDS created a new ethical wrinkle in clinical trials. There were still concerns about researchers exploiting the poor, but now there were also concerns about the rich and powerful buying their way into experiments.

"People thought 'this is my only chance,' which is not how we want research to work," Zoloth said, stressing that phase one or two trials are too preliminary to be considered treatment. "The people who had first access in [successful] trials had treatment first."

The rules the FDA and the Office for Human Research Protections use to judge the humaneness of clinical trials then had to be modified to reflect this moral tightrope.

"You have to make sure they don't use the bodies of the poor to experiment on," Zoloth said. "And you have to make sure you don't give preferential treatment to the rich."

Back to stem cells

To expand the metaphor, researchers must not only walk this tightrope, but they must do it in a packed arena with all eyes on them.

Much of the popular media coverage related to embryonic stem cell research has related to the source of the cells, human embryos that cannot continue their development after the cells are harvested. Some say the four-to-five-day-old embryos are people, therefore harvesting stem cells is murder. Others say the hollow ball of cells - called blastocysts - cannot be considered people.

However, Zoloth said that debate is only the beginning.

"It's not the only moral issue. It's not the only bioethical hurdle we have to reflect on," said Zoloth.

The debate on whether the blastocysts are people, though, will always be in the background during clinical trials, Dinsmore said.

Although the company's therapy for retinal degeneration uses embryonic stem cells gathered through a process that lets the embryo continue developing, he said critical eyes will be watching any tests in humans.

"It's a difficult position to be in when there will be so many people to criticize if anything goes wrong," Dinsmore said. "It will take longer than with other kinds of therapies."

Advanced Cell Technologies wants to put a small number of stem cells - a million or two versus the billions of cells that might be used in heart or diabetes therapies - into the eyes of people suffering vision loss from retinal degeneration.

One of the risks that concerns the FDA is cancer. As the stem cells grow and differentiate into more specific cell types, the risk of the cells causing tumors goes down. In other words, the earlier cells that prove more promising in research also cause more cancer concerns for the FDA and researchers.

"When you're putting cells into the body, you could potentially be putting a tumor-causing cell into place," Dinsmore said.

This might sound dangerous, but it is par for the course in any clinical trial, Dinsmore said. There are always risks with any therapy - cellular, chemical or other - especially in the first round of human tests.

"You define a population for whom the risk is justified," Dinsmore said.
His company is looking for people suffering partial or full vision loss.

"You don't pick people [for clinical trials]. You set a set of entry criteria that defines the type of patient you will accept," Dinsmore said. "It's set in conjunction with the hospitals where the studies are being conducted, with FDA oversight as well, so it's a group effort."

The long-standing debate about the use of embryonic stem cells should mean that care be given when choosing what therapies to pursue, Zoloth said. It's not only a matter of determining who is eligible for a trial, she said. It's also determining what trials are worth starting.

"To use stem cell technology to treat wrinkles or to cure baldness would be a trivial use of a serious technology," Zoloth said.

To Dinsmore, any upcoming clinical trial would, at the end of the day, just be another clinical trial.

"The problem is, I don't see that these [issues] are unique to stem cells. It's part of any clinical test. To an extent, these things have been hyper-extenuated to a degree where I feel it's no longer appropriate," Dinsmore said.