UWA researchers are reprogramming reactive astrocytes into functional neurons to help people with spinal cord injuries.
People with spinal cord injuries suffer significant loss of neurons at the site of their injury, followed by a cascade of degenerative problems, such as formation of de-cellularised and necrotic regions, tissue displacement and physiological changes that lead to an environment that inhibits neuronal growth.
Now, a pre-clinical study led by Assoc. Prof. Stuart Hodgetts, from the University of Western Australia and the Perron Institute for Neurological and Translational Science is testing a novel approach to create new neurons at the site of injury for these patients.
The research project is the first to elucidate a clinical treatment to treat neuronal loss after spinal cord injuries.
About the research
The basic idea is to re-program reactive astrocytes into functional neurons, right at the site of the spinal injury. Normal astrocytes, which outnumber neurons by fivefold, have multiple essential physiological functions within the nervous system. However, reactive astrocytes undergo morphological, molecular, and functional changes in response to environmental stress coming from disease or injuries. These reactive astrocytes have been shown to lose their beneficial functions and may contribute to the development of neurological diseases.
In their study, Prof Hodgetts is injecting viral vectors carrying a gene with instructions to reprogram reactive astrocytes into new, functional replacement neurons. “Our work currently involves development of a gene therapy strategy to reprogram reactive astrocytes immediately surrounding and within the spinal cord lesion into functional neurons as an alternative therapeutic approach for regeneration of functional tissue in the injured spinal cord,” Assoc. Prof. Hodgetts told Medical Forum.
The study is currently testing their novel gene therapy approach into animal models of spinal cord injuries. “…we will use this vector technology to drive the production of new neurons in the adult rat spinal cord after cervical and thoracic contusion and hemisection SCI,” Assoc. Prof. Hodgetts explained. The team will then determine if the treatment led to any improvements in the locomotor functions of the animals’ forelimbs and hindlimb.
Preliminary work has shown that the novel gene therapy approach can create fully functional neurons at the site of injury, a feat never accomplished before. “Remarkably, the result is reported to be the direct trans-differentiation of these glial cells into functional neurons, neurons that potentially can integrate into circuitry with resultant functional change,” he added.
The results of this study hold great promise to advance our understanding of cell reprogramming technologies as a potential therapy in spinal cord injuries.