Mapping the Way to More Treatment Options for Spinal Cord Injury

By Thomas Crocker
Wednesday, March 11, 2020

A dearth of therapies to repair spinal cord damage and reverse paralysis following spinal cord injury spurred a team of researchers to embark on an ambitious project to map the spine as never before.

Typically the result of motor vehicle accidents, falls or recreational activities, spinal cord injuries often occur when vertebral fragments destroy axons — portions of nerve cells that serve as two-way message highways along the spinal cord and facilitate communication between brain and body. The effects of a spinal cord injury depend on the location and extent of the damage. Nearly half of spinal cord injuries are complete, resulting in total paralysis below the level of the injury, according to the American Association of Neurological Surgeons (AANS). Incomplete spinal cord injuries cause partial loss of motor and sensory function.

The United States may be home to as many as 450,000 spinal cord injury survivors, according to the National Spinal Cord Injury Association. The AANS estimates that 17,000 new spinal cord injuries occur in the U.S. every year, with potentially devastating consequences for patients and caregivers and at great cost to the healthcare system. Many individuals living with spinal cord injuries must cope with long-term complications, such as chronic pain or bowel and bladder dysfunction, according to the National Institute of Neurological Disorders and Stroke. A method of repairing injured spinal cords remains elusive, so treatment for spinal cord injuries often focuses on rehabilitation and mitigating complications.

Researchers and clinicians still have much to learn about the spinal cord, including its anatomy. A team of researchers at the Seattle Science Foundation believes that unlocking the spinal cord’s mysteries is key to finding a way to heal it. The group is in the midst of a five-year, $15 million project to create a novel, open-access, 3D spinal cord atlas that will serve as a resource for researchers developing new therapies.

In a 2018 essay for STAT, research team members Marc Moisi, MD, Chief of Neurosurgery at DMC Detroit Receiving Hospital, and R. Shane Tubbs, PhD, Chief Scientific Officer at the Seattle Science Foundation — along with foundation ambassador Ricardo Lockette, a former professional football player whose career ended as a result of a spinal cord injury — wrote, “One thing holding back the development of new treatments is a detailed atlas of the spinal cord. With a clearer understanding of this vital tissue at the macroscopic and microscopic levels, clinicians could better treat the complex chronic conditions linked with spinal cord injury.”

Three Phases

Work on the spinal cord atlas will take place in three phases. Currently in progress, Phase 1 involves mapping the spinal cord at the macroscopic level. Using high resolution and depth-of-field techniques, researchers are digitizing the spinal cord and blending focal stacking, image stitching and 3D depth maps to reveal the spinal cord in exquisite detail.

In Phase 2, the team will use high-powered microscopy to map the anatomy of cells and tissues. The spinal cord atlas project will culminate with Phase 3, during which the team will synthesize the data from the first two phases to create a comprehensive, virtual atlas of the spinal cord that will be accessible online. With this tool, researchers and clinicians will be able to peer inside the spinal cord for a 3D, layer-by-layer view of the tissue at every point along its length. The Seattle Science Foundation envisions the finished atlas as a kind of GPS to help users explore and orient themselves in the spinal cord.

“This atlas will yield highly specific views of each layer of the spinal cord and its microcircuitry. That will give researchers and physicians greater knowledge of the precise areas of the spine that control specific muscles and functions,” wrote Drs. Moisi, Tubbs and Lockette for STAT.

A Potential Catalyst for Innovation

The atlas developers believe it could help researchers develop stem cell therapies to repair the spinal cord or allow for electrodes to be precisely placed to activate certain muscles, enabling recovery of movement below the level of a spinal cord injury.

In a 2018 interview, Seattle Science Foundation President and CEO Rod Oskouian, MD, told Life Science Washington’s News Beat newsletter, “Direct electrical stimulation of deep brain structures for such diseases as epilepsy and movement disorders like Parkinson’s disease is now an everyday occurrence. Therefore, with a new and better understanding of the spinal cord as afforded by the new 3D Atlas of the Spinal Cord, such direct stimulation of the spinal cord might be considered for various diseases that were once considered untreatable.”

Stem Cell Therapies Show Promise

In a 2019 review of stem cell therapies for acute spinal cord injuries in the Journal of Neurosurgery, a group of Stanford University researchers concluded that these therapies have the potential to reverse paralysis, and that treatments using biomaterials, such as scaffolds, to supplement and support implanted stem cells exhibit promise.

“While more extensive validation is required before transitioning cell-based therapies into the clinic, current results and ongoing efforts suggest that stem cell-based approaches may play a major role in improving acute [spinal cord injury] therapy,” the researchers wrote.

Stem cell therapies may represent the future of spinal cord injury treatment, but in Japan, they’re also the present. In a controversial and first-of-its-kind step, in early 2019, the Japanese government approved a stem cell therapy to treat spinal cord injuries following a clinical trial in which researchers used patients’ own mesenchymal stem cells to partially restore motor and sensory function, according to Nature. The journal reported that researchers not involved with the study criticized the decision to approve the therapy for clinical use because the trial was not double-blinded, making it difficult to determine the true effects of the treatment or whether the risks outweighed the benefits.