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FEATURE STORY

THE TIME IS NOW
“In the middle of every difficulty lies opportunity.” – Albert Einstein

by Steve Cox

On the evening of Tuesday, July 24, former motocross champions David Bailey and Ernesto Fonseca hosted an event at the Oakley headquarters to support Stem Cell Research being done at the University of California, Irvine, by Hans Keirstead. Keirstead is the co-director of the Sue and Bill Gross Stem Cell Research Center and associate professor in the Reeve-Irvine Research Center at UC Irvine, and he is a pioneer in the use of human embryonic stem cells in the study of spinal cord injuries. Keirstead's laboratory was the first in the world to develop a method to restrict human embryonic stem cells so they generate large amounts of only one cell type in high purity. That type of cell, an oligodendrocyte, insulates connections in the spinal cord, allowing for the conduction of electricity. The treatment has improved mobility in rats with spinal cord injuries, and it now is in development for clinical trials.

On July 24th, Keirstead put together a 50-minute presentation on his research, both past and present, and what he hopes to accomplish in the future in regard to victims of paralysis. What he presented was stunning.

“I’ve really been captured by the hope that exists in this field, I really have,” Keirstead said in his presentation. “I get to see day-in and day-out how difficult it is, but what progress is actually being made. When I was in my graduate degree, the textbooks read that there was no elasticity in the central nervous system, that the CNS could not be repaired, and that nobody had succeeded in repairing the central nervous system. Nobody had shown that a cut spinal cord or a cut brain cell could actually re-grow and functionally connect. I grew up in this environment where it was impossible to do it. I don’t know if I was dropped as a kid or what, but I just couldn’t see that that was the case and I’ve just held a surety in me that we would get there. And I think that the difference couldn’t be more palpable than in talking to my students, for example... They are going through their degrees knowing that not only is it possible, but it’s just a matter of time... We’re not there yet, but we’re very, very close.”

Over the ensuing 50 minutes, Keirstead detailed the challenges in confronting spinal-cord injuries, the different types of spinal-cord injuries, and more than anything, the difference time can make in the treatment of such an injury. He detailed the difference between an acute injury (an injury that occurred hours to days ago), a sub-acute injury (days to weeks) and a chronic injury (weeks to years), which is the definition of the injury of every effected person in attendance at the event.

Keirstead then explained that he has structured his research to deal with the injuries in that order over the last seven years at UCI, starting with acute injuries, then moving on to sub-acute injuries, and then finally to the biggest challenge, chronic injuries.

He showed how he has been able to successfully treat acute paralysis in mice by halting the secondary damage that is typical in a spinal-cord injury by blocking a molecule that is released by the bloodstream immediately following the injury. All it takes is the injection of a drug into the blood stream within 12 hours of injury that binds up the molecule, which results in a halt to the secondary damage that the body delivers upon an injury site. The result is that the injured, but treated, mouse functions just like a non-injured mouse. He also said that this same drug has shown to halt Multiple Sclerosis in two different animal models.

The next step was to generate a human antibody, and $9 million and five months later, it was shown that the human antibodies functionally worked the same for humans as the mouse ones did for mice. The clinical trial on this drug started in January of 2006 and is being tested in people. Keirstead said he wasn’t allowed to indicate how well it’s doing in people, but would only say that he’s “really excited” about it.

Next, Keirstead focused on the sub-acute injuries and tried to develop a treatment there. To do that, he and his team ventured into human embryonic stem cells. Keirstead decided to take the stem cells and make them into a particular type of spinal-cord cell to treat spinal-cord injuries, and he was successful.

Keirstead’s lab is one of very few in the world that operates unrestricted by the federal government in its work on human embryonic stem cells, mostly by operating through donations.

“This is the most powerful nation in the world for research,” Keirstead said. “More scientists than any other nation, and more money – at a greater percentage of GDP [Gross Domestic Product] – on research, yet we’re crippling what is the only medical advancement in the history of humankind that has the potential to treat every single human disease, because you are made from stem cells – human embryonic stem cells. We obgtain these cells from fertility-clinic discards. Pre-mom and pre-dad go into a fertility clinic and she takes a super-ovulation drug to generate 15 or so eggs that month instead of one, and they get pulled out of her and put in tubes, and he donates a few million sperm, and they are united. About 10 of the eggs get fertilized, so about five to seven days, or three to five days later, you get a structure called a blastocyst. You are made from the cells inside, and therefore we know that human embryonic stem cells can make every single tissue type. That is why they’re so incredible. That’s the great potential. But they have one more incredible potential, and that is the fact that they divide better than anything on the planet. There is no other cell type that divides like a human embryonic stem cell. Not any cell in your body. Not adult stem cells, not umbilical cord, not amniotic fluid stem cells... only human embryonic stem cells. They’re the only cell type where one becomes two, becomes four, becomes eight, becomes 16, becomes 32, ad infinitum... The supply and demand issue of human tissues has been solved. There isn’t one anymore. Human embryonic stem cells provide an unlimited source of human tissue.”

So the thing about human embryonic stem cells is that they can be made into anything. The first thing that Keirstead chose to make them into was spinal-cord cell types that could treat spinal-cord injuries. He was successful, and was also successful in transplanting these cells (human cells, not rat cells) to injury areas on rats that suffered sub-acute injuries and restoring their ability to walk after paralysis.

With success in treating sub-acute injuries, the technology has, like the treatment for acute injuries, moved on past the discovery process into the process of implementation, and it is going to the FDA for final approval at the end of this year and heading on to clinical trials in 2008.

However, the process for treating chronic injuries, like that of Bailey’s, Fonseca’s and many, many more, is much more complicated, and that’s what this presentation was ultimately about. Keirstead explained that chronic injuries involve a lot of scar tissue around the nerves that stop the relay of electricity down the spinal cord.
Keirstead also explained his process for restoring motor function to victims of chronic paralysis by making embryonic stem cells become a different cell type than the one that he generated for sub-acute injuries.

With the success of Keirstead’s past work, and his new method of making cells suitable for the treatment of chronic spinal cord injuries, suffice it to say that for the first time it is a realistic possibility that a treatment for victims of chronic paralysis may be coming. “The new treatment that we are developing is specifically designed for the chronic case – people who have been in chairs for years or decades,” Keirstead said. “What do I expect the result of this treatment to be? I would like it to be that every single moving muscle group in the body is re-innervated, but I will be happy if we could restore function to those few muscle groups that are most important to the life, and lifestyle, of the patient”.

And this is where you come in. Because of the lack of federal funding for this research, it can only be done through private donation. Right now, the treatment sits in a gray area between discovery and implementation. The discovery has been made, and once it has been perfected to the point of implementation, Keirstead expects that a corporation will jump in to bring it to market. Keirstead said that the research still needs about $1,500,000 to make this treatment a reality.

To make a fully tax-deductible donation, checks should be made payable to: UCI Foundation (in the memo section, please write “Keirstead Lab – Unrestricted”).

Mail to:

Attn: Tania Cusack
Reeve-Irvine Research Center
University Of California, Irvine
2107 Gillespie Bldg.
Irvine, CA 92697-4292

Thank you Steve for attending and for this piece and thank all of you who choose do donate or simply spread the word about where things stand in science right now and potentially treating an injury that ruins lives. Hope is essential and until recently it didn't exist. Together we can make a difference.

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Photo by Lex of me and Hans.