NEW ORLEANS—AxoSim Inc. recently announced an exclusive license from Johns Hopkins University to intellectual property underlying the “Mini-Brain” technology, which uses induced pluripotent stem cells (iPSCs) to create functional models of the human brain. The technology enables researchers to study key brain functions, test new therapies and screen for toxic substances at an early stage of research in human rather than animal models.
“Acquiring rights to the intellectual property underlying the Mini-Brain technology is a major step forward in our drive to transform neurology drug research,” says Dr. Lowry Curley, CEO of AxoSim. “The Mini-Brain technology complements our innovative Nerve-on-a-Chip platform and accelerates our strategy of providing the broadest and most scientifically robust neuroscience models to our growing roster of biopharmaceutical partners.”
The Mini-Brain platform is intended to allow researchers to skip much of the animal testing that is poorly predictive of therapeutic outcomes in people and move right to human clinical testing, with great gains in speed, efficiency and ultimately new drug efficacy.
“Dr. Thomas Hartung of Johns Hopkins, who led the team that developed the Mini-Brain technology, is one of the key opinion leaders in the field of microphysiological systems. His Mini-Brain technology is the most reliable and advanced platform to recapitulate the human central nervous system,” Curley adds. “An important link between the Nerve-on-a-Chip and Mini-Brains is that each was the first ever to show mature myelination in a microphysiological model of the peripheral and central human nervous systems, respectively, a critical feature for the study of neurological diseases. The scientific potential of building on this link was so apparent that when members of our senior teams first met at a major scientific meeting, there was immediate interest in working together.”
Almost 90 percent of drugs that look promising in animal models fail in humans, driving up the average cost and time to develop a new drug to an estimated $2.6 billion and more than 10 years. The problem is especially acute for neurological disorders like Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis, where animals are notoriously poor predictors of human outcomes. The recent clinical trial failures of prospective Alzheimer’s drugs highlight the need for better and earlier ways to test drug candidates.
“Currently, there is a major disconnect in drug development between data generated during preclinical testing and the outcomes seen in human clinical trials. Simply put, animal biology is not human biology. Currently, animal testing remains the gold standard in the development of new drugs, despite the historical 89-percent failure rate of new drugs advanced into clinical testing based on positive animal and other preclinical data. Neurological drugs fail at an even higher rate: an estimated 94 percent,” Curley remarks. “AxoSim’s patent-pending Mini-Brain platform predicts human results, giving researchers a much better readout of which drugs are strong candidates for costly and time-consuming clinical testing, and it does so early in the development process.”
Related Nerve-on-a-Chip technology developed at AxoSim has been shown to achieve research milestones at a fraction of the time and cost of animal testing.
“While our Nerve-on-a-Chip platform is a powerful way to assess how investigational drugs, chemicals and other factors affect human spinal and peripheral nerves, our Mini-Brain platform is a functional model of the human brain. It contains different types of crucial neuronal cells and support cells, as well as the neuron insulator myelin. The Mini-Brain platform is the only commercially available model of the brain with functional human myelin, which is critically important because disruption in myelin has implications in numerous pathologies,” states Curley.
The Mini-Brain platform creates tiny brain-like organoids for neuroscience research using human iPSCs stimulated in the laboratory to grow into brain cells, which are engineered to reproducibly form uniform spheres barely visible to the human eye. The Mini-Brain components interact with each other and their environment, and can be replicated on a large-scale. The cells used to create iPSCs can be harvested from healthy individuals or from volunteers with certain genetic traits or diseases, allowing the creation of Mini-Brains designed to study specific conditions.
As Curley points out, “there is evidence that the inclusion of microglia in the Mini-Brain expands the capabilities of the platform to address neuroinflammatory disorders, which are increasingly seen as possible contributors to neurodegenerative diseases. The use of cells taken directly from consenting patients who have the diseases we research to create Mini-Brains furthers our ability to model diseases with genetic components, such as Alzheimer’s disease and amyotrophic lateral sclerosis. We believe that the Mini-Brain platform has broad potential to address a wide variety of neurological diseases.”
AxoSim mentioned that Hartung will serve as a consulting vice president of scientific affairs. Hartung is the Doerenkamp-Zbinden Chair for Evidence-based Toxicology and director of the Center for Alternatives to Animal Testing at the Johns Hopkins Bloomberg School of Public Health. AxoSim also reported its acquisition of all the assets of Organome Inc., a company founded by Hartung to commercialize the Mini-Brain technology and other functional organ equivalents.
“It is our intention to expand this platform to ultimately address virtually all serious diseases involving the nervous system,” concludes Curley. “We intend to focus on several high-priority areas at first and add different disease capabilities as we grow. Dr. Hartung’s lab has validated the Mini-Brain as a platform for studying neurotoxicity and multiple sclerosis, which are also AxoSim’s primary initial applications.”