UCI Reeve-Irvine researchers identify novel combination treatment
A therapy combining salmon fibrin injections into the spinal cord and injections of a gene inhibitor into the brain restored voluntary motor function impaired by spinal cord injury, scientists at UC Irvine’s Reeve-Irvine Research Center have found.
Oswald Steward is director of the Reeve-Irvine Research Center at UCI
Image: UC Irvine
In a study on rodents, Gail Lewandowski and Oswald Steward achieved this breakthrough by turning back the developmental clock in a molecular pathway critical to the formation of corticospinal tract nerve connections and providing a scaffold so that neuronal axons at the injury site could grow and link up again.
Results appear in the July 23 issue of The Journal of Neuroscience.
The work expands on previous research at UCI. In 2010, Steward helped discover that axons flourish after the deletion of an enzyme called PTEN, which controls a molecular pathway regulating cell growth. PTEN activity is low during early development, allowing cell proliferation. PTEN subsequently turns on, inhibiting this pathway and precluding any ability to regenerate.
Two years later, a UCI team found that salmon fibrin injected into rats with spinal cord injury filled cavities at the injury site, giving axons a framework in which to reconnect and facilitate recovery. Fibrin is a stringy, insoluble protein produced by the blood clotting process and is used as a surgical glue.
“This is a major next step in our effort to identify treatments that restore functional losses suffered by those with spinal cord injury,” said Steward, professor of anatomy & neurobiology and director of the Reeve-Irvine Research Center, of the current findings. “Paralysis and loss of function from spinal cord injury has been considered irreversible, but our discovery points the way toward a potential therapy to induce regeneration of nerve connections.”
In their study, he and Lewandowski treated rodents with impaired hand movement due to spinal cord injury with a combination of salmon fibrin and a PTEN inhibitor called AAVshPTEN. A separate group of rodents got only AAVshPTEN.
The researchers saw that rats receiving the inhibitor alone did not exhibit improved motor function, whereas those given AAVshPTEN and salmon fibrin recovered forelimb use involving reaching and grasping.
“The data suggest that the combination of PTEN deletion and salmon fibrin injection into the lesion can significantly enhance motor skills by enabling regenerative growth of corticospinal tract axons,” Steward said.
According to the Christopher & Dana Reeve Foundation, about 2 percent of Americans have some form of paralysis resulting from spinal cord injury, due primarily to the interruption of connections between the brain and spinal cord.
An injury the size of a grape can lead to complete loss of function below the site of occurrence. For example, an injury to the neck can cause paralysis of the arms and legs, an absence of sensation below the shoulders, bladder and bowel incontinence, sexual dysfunction, and secondary health risks such as susceptibility to urinary tract infections, pressure sores and blood clots due to an inability to move the legs.
Steward said the next objective is to learn how long after injury the combination treatment can be effectively administered. “It would be a huge step if it could be delivered in the chronic period weeks and months after an injury, but we need to determine this before we can engage in clinical trials,” he said.
Lewandowski is a project scientist in the Reeve-Irvine Research Center. The study received support from the National Institutes of Health (grant R01 NS047718) and donations from Cure Medical and Unite 2 Fight Paralysis.
About the Reeve-Irvine Research Center: The mission of the Reeve-Irvine Research Center is to find new treatments for spinal cord injury through the collaborative research and educational efforts of prominent scientists and clinicians both at UCI and around the world. For more information, visit www.reeve.uci.edu.
About the University of California, Irvine: Founded in 1965, UCI is ranked first among U.S. universities under 50 years old by the London-based Times Higher Education and is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Currently under the leadership of interim Chancellor Howard Gillman, UCI has more than 28,000 students and offers 192 degree programs. Located in one of the world’s safest and most economically vibrant communities, it’s Orange County’s second-largest employer, contributing $4.3 billion annually to the local economy.
Media access: UC Irvine maintains an online directory of faculty available as experts to the media at today.uci.edu/resources/experts.php. Radio programs/stations may, for a fee, use an on-campus ISDN line to interview UC Irvine faculty and experts, subject to availability and university approval. For more UC Irvine news, visit news.uci.edu. Additional resources for journalists may be found at communications.uci.edu/for-journalists.
Tom Vasich | Eurek Alert!
Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University
Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News