This year the Spinal Research network meeting held in London on September 6-7 2019 featured an exciting programme. Here below is my summary and discussion of my chosen highlights that hold the promise to accelerate repair and recovery in patients with spinal cord injuries sooner or later.
The first day featured interesting talks showing the possibility to control the growth of an axon by promoting growth cone extension (Frank Bradke) or by increasing the trafficking of proteins important for regeneration (James Fawcett). While these are still experimental approaches using gene transfer or pharmachology in rodents that need further validation in non-human primates, they seem to be heading in the right direction.
Another exciting talk was the one on human brain and spinal organoids by Andras Lakatos, where it was shown that corticospinal tracts of human neurons could be modelled in these organised 3D culture conditions called organoids. Specific lesions of the corticospinal tracts in these human organoids will allow assessing their regenerative ability and they will represent a new model to study repair strategies that will surely develop very quickly in the next few years. One of the main outstanding challenges remaining is the need to build vasculature and the full cellular variability around neuronal circuitry. Once these hurdles are conquered- organoids will become very useful model of human disease including of spinal cord injury.
The afternoon session showcased an intriguing series of talks about the role of the systemic immune response, of liver metabolism and of the gut microbiome upon repair, plasticity and regeneration following spinal cord injury.
Jan Schwab showed how the systemic immune response and the control of infections are important variables for the clinical outcome in patients after spinal cord injury. The pharmacological and clinical management of these factors promise to facilitate repair and recovery in spinal injury patients. Similarly, Dana McTigue reported that liver metabolism following spinal injury in patients and animals influences the repair process after injury. Promoting a healthy liver can limit metabolic toxins and aggressive immune responses—these approaches need to be tested in clinical trials in spinal cord injury patients. Finally, Elisabeth Serger (PhD student in my lab) reported novel data showing that a gut bacterial metabolite promotes axonal regeneration after sciatic nerve injury and enhances synaptic plasticity after spinal cord injury in mice. This represents a potential novel therapeutic molecule since it is very safe and can be given orally but it needs much more extensive validation in spinal cord injury models in animals including with behavioural assessments before we can re-assess its clinical potential.
The day ended with a very engaging and exciting lecture by Gregoire Courtine. Gregoire summarised the state of the art of biotechnologies including the use of prosthetics, epidural stimulation and wireless systems that combine the monitoring and delivery of neurorehabilitation and epidural stimulation in spinal cord injury patients. These combinatorial strategies led to significant motor improvement in chronic spinal cord injury patients. However, these remarkable results, mostly benefit incomplete spinal lesions, while patients with complete or very severe motor impairment do not benefit as much. Work needs to be done to address these patients. A possible avenue ahead would be to combine ways to enhance axonal regrowth and connectivity such as with pharmacology, gene therapy or stem cells with these neurotechnology.
Saturday featured a very elegant talk by Joost Verhaagen that presented the latest development in gene therapy technologies to foster axonal regeneration by inhibiting scar molecules or by promoting neuronal intrinsic regenerative ability. He showed new vectors that can be controlled in space and time with robust specific expression of the therapeutic gene. These developments are a very important step towards the use in the clinic where gene therapy is used in some diseases already.
The last few important talks I would like to bring to your attention are about biomaterials and stem cells. Jacob Koffler (senior researcher in Marc Tuszynski’s lab) talked about recently developed strategies to use printed 3D spinal scaffolds made out of biomaterials that allow regeneration of stem cells axons in both rodents and non-human primates. These data showed a substantial growth of transplanted stem cell axons across these scaffolds including some growth of host axons. The level of neurological recovery was however still modest suggesting that their design might need improvements. All together, these strategies seem of very high clinical relevance since data have been reproduced across models and species. I am looking forward to seeing the first clinical trials, perhaps with an improved version of these biomaterials and hopefully in chronic patients.
Hideyuki Okano and Michael Fehlings concluded the series of presentations by presenting data in animal models of spinal cord injury with the use of human derived pluripotent stem cells and of neural stem cells respectively. Hideyuki showed that it is possible to promote repair and functional recovery in rodent models of spinal cord injury by using human derived neurons, although the degree of recovery was still limited. Michael reported interesting data aimed at characterising the biology of transplanted neural stem cells that will help us better exploit their repair potential. In fact, the field of stem cells will benefit from a better understanding of the mechanisms regulating their cellular identity once cells have been transplanted into the injured. This will be essential to allow researchers finding ways to improve their ability to form new functional circuits that underpin neurological recovery.