Building on collaboration and inspiring a new generation of investigators

The Reeve Foundation created the International Research Consortium on Spinal Cord Injury to forge a collaborative alliance among top neuroscience labs in the U.S. and abroad.

The six Consortium labs are run by scientists who, individually, have helped shape the field and made important contributions that form the basis for many potential treatments.

As a group, the principal investigators of the Consortium comprise a formidable team, combining their broad expertise and sharing their tools.

The Consortium is also helping to launch the next generation of spinal cord scientists who will carry forward the Reeve Foundation mission.

Post-doctoral fellows assigned to the Consortium are uniquely immersed in the cross-lab model of sharing. When they “graduate” and open their own laboratories, they already have a worldwide research network in place and access to renowned resources and expertise. Best of all, they have matured in a culture of collaboration.

Anderson Laboratory

Aileen Anderson, Ph.D., University of California, Irvine, California

The Anderson laboratory at the University of California Irvine (UCI) studies spinal cord injury and repair along two opposing processes: degeneration and regeneration of nerve cells

Dr. Anderson and her team ask the question, what is the role of inflammation in degeneration and regeneration?

We know that injury triggers inflammation, which in turn activates the immune system to clear damage from the injury site. But this so-called complement cascade may go too far, affecting healthy spinal cord cells important for sensation and function. In animal models of spinal cord injury, the Anderson team has shown that complement pathways can be muted to preserve spinal cord integrity. This approach may lead to potential treatments and therapies.

Anderson’s group also focuses on the role of adult human stem cells to promote recovery following spinal cord injury. Based on Anderson’s preclinical studies of stem cells, the U.S. biotech company Stem Cells, Inc. conducted a Phase I/II clinical trial in 2011 at the University of Zurich. The trial assessed both safety and effectiveness in 12 research participants between three and 12 months post-injury.

The trial has since expanded to a Phase II study called Pathway, enrolling 52 more participants with chronic cervical injuries up to two years post-injury.
Before forming her own lab, Anderson was an Associate in one of the original Consortium laboratories. In 2001, she became the scientific director of the Reeve Foundation's Animal Core Laboratory at UCI. The Core is a shared resource with other labs that facilitates research in animal models of SCI.

Fawcett Laboratory

James W. Fawcett, Ph.D., University of Cambridge, Cambridge, UK

Dr. Fawcett began his career as a physician, working in the autoimmune disease area, including difficult conditions such as systemic lupus. He did not see the field progressing so he decided to pursue research and chose neuroscience.

The Fawcett laboratory is located at Addenbrooke’s Hospital at the University of Cambridge, in England, and is part of the Center for Brain Repair, an institute formed in 1995 and funded by the British Medical Research Council.

The Fawcett laboratory focuses on the environment around a damaged spinal cord cell.

After injury, an axon may attempt to grow but is trapped in what is called the extracellular matrix, a no-man’s land for neurons. This matrix contains molecules that block axon regeneration, particularly sugar-chains called chondroitin sulphate proteoglycans. The proteoglycans form scars that seal off the area of injury, and therefore impede axon growth.

Fawcett found that these scars can be digested with an enzyme called chrondroitinase. Once the scar is neutralized, a significant amount of growth and recovery occurs. Chondroitinase doesn’t just bust the scar, it appears the drug also stimulates growth of nerve cells (plasticity).

Dr. Fawcett suggests the drug activates nerve fibers to sprout above and below a spinal cord lesion, creating new “bypass” connections. Since activity amplifies plasticity, these connections appear to improve when combined with rehabilitation.

The Fawcett lab has a patent on using chrondroitinase for axon plasticity. The hope is to move forward with clinical trials once regulatory and safety tests are done, including finding an effective way to deliver the enzyme to patients.

Moritz Laboratory

Chet Moritz, Ph.D., University of Washington

Dr. Moritz is an associate professor in the Department of Rehabilitation Medicine at the University of Washington. He also co-directs the Center for Sensorimotor Neural Engineering, a research partnership with Massachusetts Institute of Technology and San Diego State University.

Dr. Moritz’s primary research interest is “hotwiring” the damaged nervous system to restore voluntary control of movement to paralyzed limbs.

Much of his work has focused on engineering solutions, including brain-machine interfaces, “neural detours” and neuroprosthetics. Trained as a biologist, however, Moritz is not strictly dealing with on-off switches. His lab is focused in four main areas: restoration, reanimation, repair and rehabilitation.

Moritz and his group record neural messages from intact areas of the brain cortex. These signals are rerouted to paralyzed muscles, or to the spinal cord.

The lab also studies how brain activity might be directed not just to muscle but also to the spinal cord. This would create a bypass around the damaged areas. There is evidence that these bypass signals persist after stimulation is off -- meaning that nerve plasticity is being created.

Moritz and his group are working with Consortium collaborators to combine chondroitinase and stem cell therapies with spinal stimulation in order to enhance circuit plasticity and promote long-term recovery.

The lab utilizes cutting-edge tools such as optogenetics to directly activate spinal circuits for movement; Moritz and colleagues are also appling these optical techniques to improve bladder function. Using brain activity to control the movement, Moritz also hopes to also restore sensory activity.

Pfaff Laboratory

Samuel L. Pfaff, Ph.D., The Salk Institute, La Jolla, CA

The Pfaff laboratory focuses on the embryonic development of motor neurons -- cells that transmit signals from the brain or spinal cord to muscles throughout the body in order to generate movement.

Sam Pfaff and his colleagues are focused on the development of embryonic motor neurons, cells that send signals from the brain or spinal cord to muscles in the body to generate movement. Using mouse and human embryonic stem cells, they have targeted several areas of investigation:

  • Stem cells and fate choices: How do stem cells “choose” from among a variety of fates and acquire their specific identities as motor neurons?
  • Axon guidance: How do motor axons – the slender projections from nerve cells – travel from the brain or spinal cord to their target destinations throughout the body?
  • Locomotor circuitry: How does the wiring process develop, and how is it orchestrated in such a way as to enable us to walk?

Pfaff and his colleagues have been seeking answers to these questions via mouse and human embryonic stem cell research.

Further, they have been using mouse genetics and tools such as optogenetics and gene editing (CRISPR) to study the underpinnings of the neural network known as the central pattern generator (CPG), which regulates the coordinated and rhythmic firing of motor neurons needed for walking.

A rigorous scientific way to test the function of a gene is to ask the question: What are the biological consequences of preventing that gene to function? In the spinal cord, Pfaff and his group hope to target specific genes to determine whether they help or hinder growth.

Dr. Pfaff believes that these studies will reveal the kinds of practical information needed to develop treatments for spinal cord injury, as well as for other neurological diseases.

Schwab Laboratory

Martin E. Schwab, Ph.D., University of Zurich, Zurich, Switzerland

The laboratory of Martin Schwab at the University of Zurich, Switzerland, focuses on the investigation of proteins that inhibit regeneration following spinal cord injury.

Schwab pioneered the notion that the repair of spinal cord nerves is blocked by molecules found in the insulation (myelin) of axons.

His lab identified the inhibitory molecule called Nogo and also found a way to neutralize it with antibody called anti-Nogo. This has resulted in several experimental treatment strategies aimed at enhancing recovery after a spinal cord or brain injury.

Anti-Nogo treatments have shown beneficial effects in animal models of spinal cord injury. By neutralizing Nogo, rats and monkeys with spinal cord injury or stroke experienced significant functional recovery of locomotion or skilled forelimb reaching.

From this research, Novartis conducted a Phase I human safety trial for anti-Nogo. The trial enrolled 52 acute SCI patients and evaluated the pharmacokinetics (what the body does to a drug), safety, tolerance and dosing. Further spinal cord trials are planned in addition to trials of the antibody for multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).

Schwab and his group continue to study the optimal time window for successful anti-Nogo treatments. In rodents, spinal cord nerve fibers regenerated over several millimeters after acute or one-week-delayed treatments, but they did not perform as well when the antibody treatment was initiated after two weeks.

Further, the Schwab group has found that anti-Nogo works best combined with a rehabilitative approach.