Leaving injury behind

Deirdre Newman

The spinal cord is the body’s version of Grand Central Station, a hub

of constantly percolating activity, sending impulses to the brain and

receiving impulses from it to direct to other parts of the body.

A spinal cord injury can bring this hub to a grinding halt,

rendering victims paralyzed throughout their bodies, depending on

where the injury occurs.

As treatment for such injuries evolves, minor breakthroughs are

leading the charge toward major advancements. At the forefront of the

most cutting-edge advanced work is UC Irvine, where one center has

positioned itself as a catalyst of research for treating injury and

disease of the spinal cord -- conducting a slew of projects in-house

while collaborating with leading researchers in the field, scientists

outside of the field and spinal cord injury victims.

The goal of the Reeve-Irvine Research Center is to engage this

diverse group of researchers in solving one of the trickiest

challenges of modern science.

“Spinal cord injuries are immensely complex,” said Maura

Hofstadter, director of education for the center. “It’s like a puzzle

and everyone is working on their own little piece. What we’re trying

to be here is a hub and help bring the puzzle pieces together.”

The center evolved out of admiration for Christopher Reeve by Joan

Irvine Smith. Smith, an heir to the Irvine development and a

horsewoman who owns two ranches, was impressed that Reeve never

blamed his horse after being thrown from it during a competition in

1995 that left him paralyzed. Smith offered a matching grant of $1

million to start the center.

“I was very, very grateful, not only for her generosity, but for

the reasoning behind it,” Reeve said.

In 1999, Oswald Steward was recruited to head the center. Steward,

who has a doctorate in psychobiology from UC Irvine, made the

cross-country trek from the University of Virginia, where he was

chairman of its Department of Neuroscience.

Steward is also the chairman of the Scientific Advisory Committee

for the Christopher Reeve Paralysis Foundation, which Reeve and wife,

Dana, established.

Reeve said he is impressed with Steward’s expeditious approach to

research.

“Scientists like Oz Steward believe that the mission is to solve a

particular problem as quickly as possible and then move on to

something else and as a patient advocate, I of course, appreciate

scientists like Ozzie Steward and his team at UCI that share that

philosophy that research is not an end in itself,” Reeve said. “It is

a tool to produce results and the result that we want is to relieve

the suffering of people who are paralyzed.”

Research on

the cutting edge

The 6,000-square-foot center is housed in the Gillespie

Neuroscience Research Center at the College of Medicine and employs

about 50 people.

The center encourages collaboration, cooperation and communication

and the layout is a testament to that philosophy, Hofstadter said. It

is an open space that promotes a free-flowing exchange of ideas, in

contrast to most labs that feature long quiet halls and locked doors.

Researchers use mice and rats to study nerve regeneration since

they breed rapidly and their genetics are well understood, Hofstadter

said. The tiny brains and delicate, thread-like spinal cords of these

animals are suspended in solutions in a freezer.

There are three primary researchers -- Steward, Aileen Anderson

and Hans Keirstead -- as well as graduate students, post-doctoral

students, visiting faculty and undergrads.

“We want to bring students in to pique their interest so they will

pursue spinal-cord injury [research],” Hofstadter said.

In addition to working with rats and mice, the center works with

human embryonic stem cells.

Keirstead, 35, an assistant professor of anatomy and neurobiology,

has access to five of the 63 human embryonic stem cells approved for

use in the country.

“What we have done for the first time in the world is to

differentiate the human embryonic stem cells into a specialized

sub-brain cell type thought to be necessary for repair,” Hofstadter

said.

After they are differentiated, they are transferred into animals

with spinal cord injuries.

The results have been extraordinary, Keirstead said.

Keirstead has already given two Senate pitches for funding of this

type of research. He stressed the importance of federal legislators

hearing about successful outcomes during their terms of office on

research some have supported.

The center is also one of the few labs in the world that has

obtained pure lines of human olfactory ensheathing neuroglia --

obtained from the nose -- that have shown potential for cell repair

as well, Keirstead said. Neuroglial tissue comprises the bulk of

cells in the central nervous system and provide support for the nerve

cells.

Preliminary studies have shown that paralyzed animals can walk

again after receiving these cells, Keirstead said.

Reaching out for help

In addition to the three main researchers, the center now has 14

faculty members as associates. Because UCI boasts a committed group

of neuroscience researchers, Steward wanted to pick their brains on

the topic of spinal cord injury.

One of the associates is Sue Bryant, who studies salamander limb

regeneration. Another one is Anne Calof, who works with the

development of the nervous system in humans.

“If we can figure out how we did it the first time, maybe we can

trick the body into doing it again,” Hofstadter said.

Aerospace engineer David Reinkensmeyer will soon have a space in

nearby Hewitt Hall to work on creating robots to help spinal cord

injury victims relearn how to walk. The robots will replace physical

therapists for hip and ankle support.

“When we do clinical trials with any of these treatments,

rehabilitation will be part of it,” Hofstadter said. “We’re very

excited about it.”

Steward also took the initiative to invite the California Spinal

Cord Injury Neural Regeneration Consortium, a group of about 100

scientists, to work on solving the puzzle. California has the dubious

distinction of producing the highest rate of spinal cord injuries in

the country, mostly from car accidents and surfing.

The center makes it a priority to invite feedback from the

community it was established to help. It conducts surveys asking

spinal cord injury victims what they would like to see the center

focus on. Based on the outreach, researchers found that most of what

they were emphasizing -- helping patients walk again -- is not the

foremost desire. Bladder control is, they found, and added that to

their research, Hofstadter said.

It also hosts a meet and greet with the scientists, where spinal

cord injury victims, their families and their caregivers can talk to

researchers from around the state.

And it has one other source with intimate knowledge of life after

an injury. One of the center’s own researchers, Kim Anderson, 31, was

injured in a car accident in Texas when she was 17 that rendered her

a quadriplegic. Her post-doctoral work at the center focuses on how

molecules are affected after a cervical spinal cord injury.

“I’m very driven to find treatments of any type to help people

with spinal cord injuries, especially quadriplegics, which I am,

because we have the biggest burden physically, financially and

emotionally,” Anderson said. “And I think that people with spinal

cord injuries have a great amount of information that they can give

researchers about what humans are really going through and can really

help the development of looking at outcomes when they’re looking at

clinical trials.”

Backing risky research

In 2000, the president of the University of California asked the

center to administer the California Spinal Cord Injury Research Fund

(previously the Roman Reed Bill). The Reed bill, named for Roman

Reed, a Bay Area man who suffered an paralyzing accident while

playing college football, is state-funded program that provides $1

million a year for spinal cord injury research. The center was

entrusted with developing a research program for faculty from the UC

system and the rest of California.

In line with its philosophy of attacking the puzzle from all

angles, the center disburses seed money for projects that might be

considered too uncertain by others, Hofstadter said.

“It’s a little risky, but we’ll get good information, even if [the

project] fails,” Hofstadter said.

The center gives a smaller amount of funds to the Roman Reed Core

Laboratory, which is part of the center. The goal of the lab is to

expand the number of people participating in spinal cord injury

research. To that end, it invites researchers with an interest in

spinal cord injury but who are not working in the field.

“Like a chemist who doesn’t know a rat from a dog and doesn’t know

where the spinal cord is, but wants to explore,” Hofstadter said. “We

tell them to write up a proposal, then come play with us. So a

project that would likely never happen or take years [can happen] in

three months. We’re fast-tracking ideas.”

The center is currently in a campaign to raise $2 million for

developing human spinal cord injury studies and treatments and is

about three-quarters of the way there, Steward said.

“We’re just really excited about what’s going on,” Steward said.

“It’s still a unique resource in the world.”

* DEIRDRE NEWMAN covers Costa Mesa and may be reached at (949)

574-4221 or by e-mail at [email protected].