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A test of nerves
Thomas Lane leads UCI's efforts to end the devastating effects of multiple sclerosis
Thomas Lane looks anything but the typical scientist as he strides through his lab at UC Irvine's Sue & Bill Gross Stem Cell Research Center sporting shorts, a T-shirt and loafers. Walking past research assistants hunkered over microscopes and test tubes, he pauses to show off his prized possessions: 1970s posters of the Cincinnati Reds that once adorned his bedroom in his hometown of Muncie, Ind.
That's the thing about Lane: He's just as comfortable talking sports as he is discussing stem cells. He loves baseball, swam competitively in high school and college, and is an avid surfer. In short, he's a regular guy — who has made extraordinary gains in UCI's battle against a devastating disorder with no known cure.
His low-key demeanor belies the fact that Lane belongs to a select group of researchers who've made significant advances toward understanding and treating multiple sclerosis, a chronic disease of the central nervous system that can cause blurred vision, slurred speech, numbness, acute fatigue and, in its most extreme form, blindness and paralysis.
A Chancellor's Fellow and professor of molecular biology & biochemistry, Lane has dedicated his career to studying MS. He directs UCI's new Multiple Sclerosis Research Center, built in part with a five-year award he received in 2009 from the National Multiple Sclerosis Society to develop new techniques for repairing and regenerating MS-ravaged nerve tissue.
"I want to bring research from the bench to the clinic in order to help people with MS," Lane says. "We have researchers at UCI with different approaches to the disease, and the center gives us a wonderful platform to discuss new avenues of treatment."
For example, Dr. Michael Demetriou, the center's associate director, is exploring ways to combat MS through metabolic therapy, with the hope of someday treating patients with nutritional supplements.
Lane's own research attacks MS on two fronts. In 2001, he and UCI researchers Hans Keirstead and Michael Liu stopped the disease's progress in mice by blocking the source of the nerve tissue damage. To illustrate how, Lane calls up on his computer screen an MRI scan of a normal brain with the axons — nerve fibers that conduct electrical impulses — highlighted in red.
"The green part wrapping around the nerves is the protective sheath called myelin. It's like the plastic coating you find on electrical wire," he says. "In patients with MS, the axons start to lose their protective sheathing. It's an ebb and flow that occurs throughout the brain."
As demyelination progresses and more axons are exposed over time, the disorder causes severe clinical symptoms in patients.
"In the beginning, they might experience awkward sensations in their extremities, such as tingling or numbness," Lane says. "It's when the disease goes from its relapsing-remitting stage to progressive that things go to hell. It impairs movement. Patients develop difficulty walking and can be confined to a wheelchair. Some lose their vision. And there's really no cure."
The UCI team found that they could stop the nerve damage by blocking chemokines, a class of proteins that recruit to the brain T cells that contribute to myelin destruction. A drug Lane helped create to target chemokines is now in Phase 2 clinical trials on people with inflammatory bowel disease (chemokines also have been implicated in IBD).
"IBD allows us to more rapidly determine the drug's safety and effectiveness," he explains. "We hope to expand future trials to include MS patients."
Still, it's not enough to just arrest the progress of the disease, Lane says: "I wanted to know how one could repair the damage that already has occurred. There are no therapies for restoring movement. This is why we got involved in stem cells."
His second area of research focuses on treating MS with human neural progenitor cells, which Lane has found can not only halt myelin destruction but reverse it.
He's working with Jeanne Loring, professor and director of the Center for Regenerative Medicine at The Scripps Research Institute in La Jolla. In May, the two received a $4.8 million grant from the California Institute for Regenerative Medicine to develop stem cell therapies that can be used in animal models with MS for the next phase of clinical trials.
"Collaborations are based on personalities. That's why this has been so successful," says Loring, who recognized a kindred spirit in Lane. Neither is hampered by a big ego; each insists the other is responsible for winning the grant.
"Tom and I are very similar," Loring says. "We both embrace new ideas. He was really interested in learning about human stem cells and molecular analysis, and I wanted to learn about immunology. We both care about patients and wanted to make the symptoms of MS go away."
In their first collaboration, conducted about a year ago, they injected mice paralyzed by an MS-like condition with stem cells.
"A couple weeks later, one of my postdoc students came to me and said, 'The mice are getting better.' I didn't believe her," Lane recalls. "So we walked down to the lab, and she showed me." The mice that had received the stem cells were walking slowly around their enclosure.
"We're building on very exciting data," he says. "We can transplant cells into mice with MS and get them moving again. It's pretty cool."
Loring agrees: "It was almost magical. We thought, ‘We must be onto something,' but we didn't know why the cells worked. The grant will allow us to follow up on our original study, but bring it up to the stage where we can eventually treat people."
While excited about the initial findings, Lane is a careful and cautious scientist. He doesn't want to offer false hope, noting: "What works in mice often doesn't in humans."
He often speaks to MS patients about the research being done at UCI. During a recent presentation for the San Diego chapter of the National Multiple Sclerosis Society, Lane invited the entire group to tour his lab.
"We have an open-door policy," he says. "We just want people to know we're working as hard as we can to find a treatment."
And, if they're interested, he has a few cool baseball posters to show them.
More about multiple sclerosis:
- There are about 400,000 people diagnosed with MS in the U.S., with nearly half — about 160,000 — living in California. Almost 2.5 million people worldwide have the disease.
- MS affects significantly more women than men. The disorder is most commonly diagnosed between the ages of 20 and 40, but it also can appear in young children and older adults.
- MS is not contagious or directly inherited, but researchers including UCI's Michael Demetriou have found a link between genetics and the environment in triggering the disease.
- MS occurs in most ethnic groups, including African Americans, Asians and Hispanics/Latinos, but is more common among white individuals of Northern European ancestry.
- MS is caused by damage to the myelin sheath, the protective covering around nerve cells.
- Symptoms vary, because the location and severity of each attack can be different. They include vision loss, typically one eye at a time; numbness, tingling or pain; problems with walking or coordination; and fatigue and depression.
Sources: U.S. National Library of Medicine, National Multiple Sclerosis Society
— Kathryn Bold, University Communications