Mixing it up

The ways of science often flow along mysterious routes, but few would think that solving the crippling effects of multiple sclerosis and spinal cord injuries would go the way of the martini.

But if the groundbreaking research of UCI assistant professors Tom Lane and Hans Keirstead bears out its potential, the martini will have played its role.

A little more than a year ago, Tom Lane was conducting multiple sclerosis research in the Department of Molecular Biology and Biochemistry. Across campus, Hans Keirstead was deep into his work on spinal cord injuries in the Reeve-Irvine Research Centerat the School of Medicine. Neither was aware of the other’s research.

“As assistant professors, our heads are usually stuck in the lab,” Keirstead says. “We’re totally focused on what we’re doing, on our particular projects, our potential grants and our potential outcomes. Until you have published several works and started to fulfill your potential, you have no time to come out of the lab.”

What brought them together was a seminar on spinal cord research.

“I’m a spinal cord researcher with an interest in MS and Tom is an MS researcher with a peripheral interest in spinal cords. We started talking about the middle ground and the overlap, and it was uncanny how much overlap there was,” Keirstead says. “A few good conversations, a couple of martinis and some damn good science. The process has been a blast and the product is very exciting.”

Exciting indeed.

Multiple sclerosis, which attacks the central nervous system and causes a variety of symptoms from blurred vision and poor coordination to blindness and paralysis, has affected more than 350,000 Americans, Lane says. While the causes and cures to the disease remain elusive, its destructive mechanisms are becoming clearer. The disease sets in motion a series of immune system responses that damage the central nervous system.

Lane’s research had centered on a process called demyelination, in which a protective sheath around nerve cells, called myelin, is destroyed. This destruction prevents the nerves from functioning properly with crippling effects. Researchers have long thought that white blood cells contribute to demyelination in MS patients by entering the central nervous system and destroying myelin. But no one was sure how the cells enter. Lane’s research has focused on the “how.” One element particular to Lane’s interest is a molecule called IP-10, which appears to play an important role in attracting white blood cells, therefore contributing to myelin destruction.

As it turns out, multiple sclerosis patients have extremely high levels of IP-10 in their central nervous systems, which Lane thought might explain the accompanying large increase in white blood cells.

“It’s like lining up dominos,” Lane says. “Once one falls, the whole line is destroyed. If we could prevent the first domino from falling, we could upset the chain of events and damage.”

So the team focused on IP-10. They infected mice with a multiple sclerosis-like disease, which left the animals crippled. They then injected some mice with an IP-10 antibody. The treated mice started walking again in a few days. Not only did the process halt the effects of the disease, it actually allowed the central nervous system to repair itself.

“One of the more interesting findings is that the central nervous system is repairable. This was once thought impossible,” Lane says.

“The results were astounding,” Lane says. “We feel this may really help people. However, we need to do additional testing before we can take our findings into the clinic.”

Following the success achieved by Lane’s model of targeting IP-10, Keirstead decided to try the technology in spinal cord injury.

“What this treatment does is alter the immune response system. A spinal cord injury triggers an immune response system that accounts for secondary damage to the original injury. If you could stop that secondary response, probably the majority of the people in wheelchairs wouldn’t be in wheelchairs — they would walk with canes or other assistance. So the potential to be able to knock down the immune response would have a tremendous effect. I started working the spinal cord side, and Tom had enormous input to that. It worked the same way, and the secondary damage was avoided.

“So now there are two applications for this treatment and possibly others, stroke being the largest one.”

The results so encouraged the unlikely pair that they have started their own company to hasten along the results.

“The reason we are starting this company is not to make cash,” Keirstead says. “We don’t want to become CEOs and run around in business suits. Tom and I are scientists. We’re going to continue being scientists. The ultimate goal of anybody in science is to see his or her science applied. All of this company business is a mechanism to provide a human reagent (a human antibody to IP-10). You need a mouse reagent to treat mice and a rat reagent to treat rats and a human reagent to treat humans.

“But just to make the human reagent takes a year and nine million bucks. Getting that through grant funding would take us 20 years. So the only route is through industry: Find some venture capital, get it working right and then partner with a pharmaceutical company. We’re focused on treating people.”

“That was one of the initial discussions: how to get it to people fast,” Lane says. “That’s when Hans suggested a company. I said, ‘Wait a minute, that’s what the other guy does. I’m a scientist, not a businessman.’ But it’s exciting. For me, this is uncharted territory.”

The young scientists have already won initial funding for their company and hope to begin initial trials of their remedy.

Their quick success would never have come about without the collaboration across research fields, the pair agrees. They hope other researchers will likewise reach out.

Just how?

“My advice?” Keirstead says, “Learn to make martinis.”