Gliomatrix™ is a mixture of olfactory ensheathing cells (OECs) and fibroblasts in a 3D scaffold. Olfactory ensheathing cells are derived from the patient’s own olfactory bulb, then co-cultured in the 3D matrix in vitro. This ATMP-HE medical product is administered to the site of the spinal cord injury in the subsequent medical procedure.
The transplant initiates the process of rebuilding of functional connections between axons located above and below the site of injury.
The expected result of Gliomatrix™ use in patients is regaining motor and sensory function, which – combined with a proprietary rehabilitation program – would allow them to significantly improve their physical activity and quality of life.
Currently, Astroglial Innovations intends to use the Gliomatrix™ product for spinal reconstruction therapy in accordance with the EMA CAT qualification for the treatment of total spinal cord injuries in humans in the ATMP-HE mode according to Polish legislation. Next, our goal will be a clinical trial and registration of the ATMP Gliomatrix™ product in a central procedure at the EMA. In the future, we plan to expand the indications for the use of the product, e.g. to include the treatment of incomplete spinal cord injuries and potentially other diseases.
Spinal cord injuries socioeconomic impact
Every year, around the world, between 250 000 and 500 000 people suffer a spinal cord injury (SCI). The estimated annual global incidence is 40 to 80 cases per million population. Up to 90% of these cases are due to traumatic causes such as road traffic crashes, falls or violence, though the proportion of non-traumatic spinal cord injury appears to be growing.
Symptoms of spinal cord injury may include partial or complete loss of sensory function or motor control of arms, legs and/or body. The most severe spinal cord injury affects the systems that regulate bowel or bladder control, breathing, heart rate and blood pressure. Most people with spinal cord injury experience chronic pain and are two to five times more likely to die prematurely comparing to people without a SCI. It is also associated with a risk of developing secondary conditions that can be debilitating and even life-threatening—e.g. deep vein thrombosis, urinary tract infections, muscle spasms, osteoporosis, pressure ulcers, chronic pain, and respiratory complications.
Unsurprisingly, SCIs are taking its toll when it comes to the mental health of patients, as well as socioeconomic costs. Spinal cord injury may render a person permanently dependent on caregivers. Assistive technology is often required to facilitate mobility, communication, self-care or domestic activities. An estimated 20-30% of people with spinal cord injury show significant signs of clinical depression, which in turn has a negative impact on improvements in functioning and overall health. Misconceptions, negative attitudes and physical barriers to basic mobility result in the exclusion of many people from full participation in society. Children with spinal cord injury are less likely than their peers to start school, and once enrolled, less likely to advance. Adults with spinal cord injury face similar barriers to economic participation, with a global unemployment rate of more than 60%.
Development of the neuroregenerative medicine
For many years it was believed that spinal cord reconstruction is impossible. In the 1980s, a group of glial cells with strong regeneration-promoting properties was described by Geoffrey Raisman to be present in the olfactory bulb. Olfactory ensheathing cells (OECs) are naturally responsible for the constant neurogenesis of the olfactory epithelium, responsible for our smelling, and for the natural restoration of injured olfactory axons, guiding them from the peripheral nervous system to the central nervous system (CNS).
Building on these promising outcomes, the research team took a significant step forward in 2012 and the performance of the first in the world surgical approach in a patient with a total transection of the thoracic spinal cord. OECs and olfactory nerve fibroblasts (ONFs) from the patient’s own olfactory bulb were transplanted into his spinal cord. Additionally, the spinal cord was reconstructed with grafts of autologous peripheral nerves. As a result, the patient – Mr. Dariusz Fidyka – regained remarkable recovery of deep and superficial sensation in his lower extremities, recovery of voluntary control of the proximal group of lower extremities, and also recovery of sexual function. Moreover, electrophysiological and radiological evidence of regeneration of nerve fibers in the human spinal cord was demonstrated.
Our continued scientific work proved for the first time in 2018 that human bulbar OECs are able to cause axon regrowth into the spinal cord, in a model of rat brachial plexus injury. Hence, we showed that the OECs-ONFs can be delivered more effectively to the spinal cord, when used in form of explants of cells suspended in an extracellular matrix.
This is how the idea of Gliomatrix™ was orignated.