It could be said that 2014 has been something of a “hope-expectation” rollercoaster for the paralysis community. A myriad of “breakthroughs” during the last 6 months have instilled a mixture of hope, cynicism and downright hysteria within the paralysis community and mass media.
Now that the dust has settled on the last two weeks, we thought it would be a great opportunity to share our thoughts about what has been a whirlwind year in the field of spinal cord injury research and what we can expect for the future.
It all started in the spring when we saw some exciting news from Louisville, Kentucky whereby 4 spinally-injured men experienced changes in autonomic and voluntary function after undertaking an epidural stimulation programme that has been championed by the Christopher & Dana Reeve Foundation.
The newspapers and media outlets were naturally all over this – “spinal cord shock helps paraplegic move legs” and “shocking study gives hope to paralyzed people” they crowed.
Once the hype had dissipated, the publication in the journal Brain showed us that the implanted epidural stimulator was able to “neuromodulate” the spared spinal circuitry to perform some voluntary activation of trunk and lower limbs when the stimulator was switched on. Impressive stuff.
Naturally, the media latched onto the “miracle” of limbs moving on command. The videos were undoubtedly compelling viewing. However, it is important to understand that the movement of the limbs was only possible when the stimulation device was switched on and that the function was not sufficient to have people up and walking voluntarily.
However, for the research community the most remarkable aspect of this study was what happened to the spinal cord when the stimulator was switched off. It was the reported changes in temperature regulation, bladder control, sexual function and reduction of episodes of autonomic dysreflexia that was described as a “happy surprise” from this study.
This has now prompted Dr Susie Harkema’s lab in Louisville to switch their outcome focus to the bladder, autonomic and cardiorespiratory function to their next cohort of 36 patients (see the Reeve Big Idea) so that they can shed some light on what is happening in the cord whilst reproducing it in a bigger group of patients. It will be intriguing to see the results from a bigger group. Though not as glamorous as walking, the possibility of controlling temperature, reducing the probability of autonomic dysreflexia and better control of the bladder could be life changing for many.
Last month, neurokinex Director, Harvey Sihota, attended the annual Working2Walk Symposium in Seattle which is run by US non-profit Unite2FightParalysis. The two-day conference showcased some of the most leading edge scientific research into cures for spinal cord injury bringing researchers, clinicians and community members together. Most importantly the entire agenda was dedicated to outcomes in chronic spinal cord injury.
Some of the highlights from the symposium included:
Dr Chet Moritz, University of Washington, presented some amazing work with brain-computer-spinal interfaces. By placing hair-like wires below the spinal lesion and stimulating movement through brain-controlled interfaces his team were able to enhance the function of spared spinal circuitry in animals. This could be real possibility for retraining and restoring voluntary hand/grasp function in tetraplegics in the future.
Ida Cahill, CEO of Conquer Paralysis Now, launched a brand new and exciting initiative called The SCI Challenge. This is a multi-million US dollar incentive prize designed to find a cure for chronic paralysis within the next decade. The idea is to incentivise researchers to find a solution to chronic spinal cord injury by offering strategically designed prizes, fostering collaboration through competition and attracting the best scientists and engineers into the field. More money, more talent and more focus can only serve the community better with regards to finding a solution to the incredibly complex problem that is chronic spinal cord injury.
Dr Jerry Silver, Case Western, presented more evidence of chronic injury recovery using combinations of peptides, growth factors, peripheral nerve bridges and the chondroitinase enzyme (something that Spinal Research UK are championing). Following on from his last publication he continued to show remarkably consistent recovery of breathing and bladder function in chronically injured rodents. Dr Silver could not hide his excitement to be collaborating with Dr Liz Bradbury, Kings College London and Dr Gregoire Courtine, EPFL, Switzerland in order to combine his approaches with their own lines of work to gain even better results in function before progressing to humans.
Dr Murray Blackmore, Marquette University, described his investigations into new genetic targets for rebooting the growth machinery of the injured spinal cord. He has most recently been leveraging data from the cancer research field and has identified additional gene targets that are responsible for the growth of cortical spinal tract axons – the ones responsible for finer motor movements. We look forward to seeing if these genetic targets could facilitate robust regeneration of the spinal cord through novel gene therapy approaches.
Dr Reggie Edgerton, UCLA, presented some further advancements of neuromodulation – the stimulation technique that was used in Louisville, Kentucky. As well as an implanted epidural stimulator he is now working on transcutaneous (through the surface of the skin) and drug-based ways of stimulating the cord. He explained how his lab is developing a new non-invasive stimulator that could be ready for market within the next couple of years. Whilst Dr Harkema has been primarily focusing on lower limbs, Dr Edgerton has also been working on upper limb circuitry. He talked about 6 tetraplegics gaining some return function in a recent study at his lab. He believes that the transcutaneous stimulator alone could have a massive impact on incomplete injuries in the very near future. This is very exciting to hear and the timelines are much closer than we could have envisaged. Two of Dr Reggie Edgerton’s former students, Dr Gregoire Courtine, EPFL Switzerland and Dr Ronaldo Ichiyama, Leeds University are also working on similar lines of science so this technology is certainly gaining some traction in Europe as well as North America.
Dr Wise Young, Rutgers University and SCINetChina, presented some preliminary information from the Umbilical Cord Blood & Lithium Phase II clinical trial that has taken place in China under his supervision. He explained that although none of the chronic ASIA A participants had improved motor scores, 15 out of the 20 patients were able to take steps with a walker whilst in rehabilitation. This “phenomena” is something that he would like to further study and has not yet been able to explain. Another “happy surprise” perhaps? Some of the participants also gained multiple levels of sensory function. Finally, there was also some anecdotal data on positive changes to neuropathic pain and bladder function but this is yet to be confirmed. In the meantime we eagerly await the publication of the trial data.
Keep an eye out on Unite2FightParalysis website and facebook page for video presentations from this year’s symposium.
Nose cell breakthrough
A day after Working2Walk, we saw UK news outlets go into a frenzy again claiming that a paralysed man could miraculously walk again thanks to stem cells derived from his nasal cavity. There was an incredible amount of publicity from even the most well-respected outlets such as BBC Panorama and The Times newspaper.
Dr Geoffrey Raisman, UCL, has dedicated much of his career to brain and spinal cord injury. His claim to fame until today has been proving that the nervous system is not hard-wired and that it is capable of changing even after injury. He coined the term “plasticity” which is widely used in neuroscience and rehabilitation today to describe the brain and cord’s ability to change itself and form new connections. His primary interest over the last decade has been olfactory ensheathing cells (OECs) – cells that assist nerve repair in the sensory system of the nose throughout adult life.
There have been a number of human trials using OECs over the last 10 years. For each trial, the cells were derived from a variety of sources before being transplanted into cord. Such examples include Dr Carlos Lima, Portugal, who transplanted olfactory mucosa from the noses of many patients with SCI and Dr Hongyun Huang, China, used OECs derived from aborted foetuses in over 1600 SCI patients. Both trials produced data showing modest recovery but these results have never really been followed up with further quantitative studies.
In this most recent case, the cells were derived from the olfactory bulb, deep in the brain. The cells were then cultured in a lab prior to being ready for transplantation. In addition to the cell transplant Dr Raisman’s Polish collaborator, Dr Pawel Tabakow and his surgical team untethered the cord from its lining, surgically removed some scar tissue from the chronic lesion and took some peripheral nerve tissue from the ankle of the patient for use as a bridge over the lesion.
It is noteworthy that the patient’s injury was not a more common contused/bruised cord, but rather a rare knife injury which happens to create a cleaner cut and scar. It’s not clear whether removing scar tissue from the lesion would ever be a viable surgical approach in a more common contused injury – especially one that is incomplete. Also, whether the cells or one of the multitude of surgical procedures contributed to the patient’s recovery is hard to deduce without there being more participants. We look forward to seeing more data from the team at UCL and Poland.
A week on and we saw that Spinal Research UK has announced £300k of funding to help researchers at Cambridge University, University of London and Kings College London collaborate to develop a human-grade form of chondroitinase – an enzyme that breaks down chronic scar tissue and increases the capacity for the cord to regenerate and rewire itself. This piece is probably the one most important development for chronic spinal cord injury in the near future and we’re delighted that Spinal Research UK is championing this. Interestingly enough, this announcement received the least news in the media yet currently holds the most promise for chronic spinal cord injury.
With all of these exciting developments, it is important that we as a community manage our expectations of timelines without losing the hope that one day we will all benefit from this great work. Science takes time. However, with more money and more talented people entering the field, we will see these lines of science reach the bedside sooner rather than later. There is a lot to be hopeful for in this field yet a lot of hard work and scientific discovery to come.
Rehabilitation is crucial
As with any of the repair strategies on the horizon, rehabilitation will always play a key role in training new functional synapses, rebuilding muscles and co-ordinating new function in order to make use of it in everyday life. If we do want to capitalise on these breakthroughs in the future, it’s important that we maintain our muscle mass, bone density and range of motion whilst continuing to stimulate the nervous system in a variety of ways. The healthier the musculoskeletal system and spared spinal circuitry, the better position you’ll be in when the breakthroughs become a reality.
This is why we feel our activity-based rehabilitation and wellness programmes will play a pivotal role in seeing these life-changing breakthroughs reach the community. Here’s hoping the rollercoaster continues into 2015 and beyond and we all get wiser to cutting through the media hype and down to the real scientific facts.
The neurokinex team