MAG

Spinal cord injuries are serious issues impacting hundreds of thousands of people in the United States. It’s estimated there are more than 17,000 new cases of spinal cord injuries each year, which can cause permanent damage in patients. With the prevalence of such injuries in the U.S., as well as the rest of the world, multiple companies are focusing their efforts on developing regenerative medicines to treat these injuries, which can result in permanent changes in strength, sensation and other body functions below the site of the injury, according to the Mayo Clinic. In addition to profound persistent neurological impairment, patients with chronic SCI suffer a variety of other health consequences including respiratory complications, cardiovascular complications, urinary and bowel complications, spasticity, pain syndromes, pressure ulcers, osteoporosis and bone fractures. According to the National Spinal Cord Injury Statistical Center, the leading cause of spinal cord injury is vehicle crashed, followed closely by falls. Other common causes of spinal cord injuries include sports injuries and acts of violence, such as gunshot wounds. Developing therapeutics to help patients regain full function are underway. BioSpace takes a look at recent work undertaken by researchers in the field: Keio University – Japanese researchers at Tokyo’s Keio University are aiming to use induced pluripotent stem (iPS) cells to treat spinal cord injuries. Until this particular study, the use of induced pluripotent stem cells had only been allowed in treating, eyes, hearts, cranial nerves and blood platelets of patients as part of regenerative medicine research. The trial will attempt to take the induced pluripotent stem cells and grow them into nerve cells. The Japanese research team will transplant two million of these new nerve cells into the injured areas of each patient via injection in hopes of inducing a response. The patients will also be given immunosuppressant drugs to prevent a rejection of the transplanted cells. InVivo Therapeutics – In February, Massachusetts-based InVivo published research data in the Journal of Neurosurgery: Spine describing the previously presented complete six-month primary endpoint results from the company's single-arm INSPIRE 1.0 study. Invivo’s biodegradable device is surgically implanted in patients who are dealing with a complete thoracic AIS A spinal cord injury. The article pointed to data that showed a probable benefit of a bioresorbable polymer scaffold for safety and neurological recovery in patients with complete thoracic spinal cord injury. InVivo has officially closed the INSPIRE 1.0 study and is actively enrolling patients into a second pivotal clinical study of the Neuro-Spinal Scaffold in patients with acute SCI, dubbed INSPIRE 2.0. Lineage Cell Therapeutics – California-based Lineage Cell Therapeutics, Inc. provided an update on its oligodendrocyte progenitor cell (OPC) therapy for the treatment of acute spinal cord injury in December. The company said it developed enhanced differentiation process, leading to major improvements in production and quality of its OPC1 cell therapy drug product. Improvements included ready-to-inject formulation of OPC1, which enables clinical use at a much larger number of spinal cord treatment centers, accelerating enrollment for a larger and potentially registrational clinical trial, the company said. The company also saw improvements in OPC1 functional activity, as assessed by cellular migration and secretion of key growth factors. OPC1 is an oligodendrocyte progenitor cell (OPC) transplant therapy designed to provide clinically meaningful improvements in motor recovery in individuals with acute spinal cord injuries. ReNetx Bio – In January 2020, Connecticut-based ReNetX Bio received Fast Track designation from the FDA for its clinical asset AXER-204 for the potential treatment of Chronic Spinal Cord Injury. ReNetX Bio is currently conducting a Phase I/II clinical trial dubbed RESET in patients with SCI. Topline results are expected to be announced this year. AXER-204 is designed to block axonal growth inhibitors in the central nervous system to promote neural repair. While Damage to axons in the CNS is permanent, ReNetx believes damaged and remaining undamaged axons provide an opportunity for restoration of function if new connections can be grown. In preclinical studies, AXER-204 has been shown to promote axonal growth and recovery of neurologic function in the central nervous system by acting as a decoy and binding the 3 key inhibitors Nogo-A, MAG, and OMgp. This interrupts their activation of NgR1 thereby promoting axonal growth. MicroCures – New York-based MicroCures’ lead product is siFi2. Preclinical research suggests that siFi2 may help overcome these natural inhibitors and trigger successful axon regeneration and reattachment at the site of injury. In preclinical studies of spinal cord injury in rats, MicroCures has demonstrated that treatment with siFi2 allowed axon growth to occur through the injury’s inhibitory barriers. Researchers did not witness similar axon growth among control animals, according to the company’s website.

More Anti-inflammatory Genes Mean Longer Lifespans For Mammals Mammal species with higher copy numbers of siglec receptor genes have longer maximum lifespans We age in part thanks to “friendly fire” from the immune system — inflammation and chemically active molecules called reactive oxygen species that help fight infection, but also wreak molecular havoc over time, contributing to frailty, disability and disease. The CD33rSiglec family of proteins are known to help protect our cells from becoming inflammatory collateral damage, prompting researchers at the University of California, San Diego School of Medicine to ask whether CD33rSiglecs might help mammals live longer, too. In a study published April 7 by eLife, the team reports a correlation between CD33rSIGLEC gene copy number and maximum lifespan across 14 mammalian species. In addition, they found that mice lacking one CD33rSIGLEC gene copy don’t live as long as normal mice, have higher levels of reactive oxygen species and experience more molecular damage. “Though not quite definitive, this finding is provocative. As far as we know, it’s the first time lifespan has been correlated with simple gene copy number,” said Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine and member of the UC San Diego Moores Cancer Center. “Since people also vary in number of CD33rSIGLEC gene copies, it will be interesting to see if these genes influence variations in human lifespan as they do in mice.” Varki led the study, along with Pascal Gagneux, PhD, associate professor of pathology. The CD33rSIGLEC genes encode siglec receptors that bind sialic acids — sugar molecules found on many cells. These siglec receptors stick out like antennae on the outer surface of immune cells, probing the surface of other “self” cells in the body. When sialic acids bind siglec receptors, they transmit the message to the inside of the cell. This signal relay puts a brake on immune cell activation. In this way, the CD33rSiglec receptors help dampen chronic inflammation and reactive oxygen species in the body. Different mammal species carry different numbers of the CD33rSIGLEC genes in their genomes. In this study, Varki, Gagneux and colleagues surveyed 14 different mammalian genomes, including those of elephants, dogs, monkeys and humans, and found that CD33rSIGLEC gene number correlates with maximum lifespan. In other words, species with more copies tend to live longer, even when the researchers controlled for other factors, such as body mass, adjacent genes and shared evolutionary history. To dig deeper, Varki, Gagneux and team turned to a mouse model. They discovered that mice that were missing one CD33rSIGLEC gene and experienced inflammation early in life showed signs of accelerated aging (gray hair, disorientation, thin skin), had higher levels of reactive oxygen species and did not live as long as normal mice. “The higher CD33rSIGLEC gene number can be thought of as an improved maintenance system that co-evolved in mammals to buffer against the effects of many infectious episodes fought off by the immune system of long-lived mammals,” said Gagneux. Study co-authors include Flavio Schwarz, Oliver M. T. Pearce, Xiaoxia Wang, Annie N. Samraj, Heinz Läubli, Javier O. Garcia, Andrea Garcia-Bingman, Patrick Secrest, Casey E. Romanoski, Charles Heyser, Christopher K. Glass, and Nissi Varki, UC San Diego; Hongqiao Lin, Xiaoming Fu and Stanley L. Hazen, Cleveland Clinic Lerner Research Institute. This research was funded, in part, by the National Institutes of Health (grants P01HL107150, P01HL076491 and RO11065732), Ellison Foundation, Mathers Foundation of New York, Novartis Foundation for medical-biological research, Cancer Research Institute and AB SCIEX. Hey, check out all the research scientist jobs. Post your resume today!