Almost 12 months on from our last research update, we decided to take some time to produce another piece to cover some of the scientific progress in 2015 – some of which has hit the headlines as well as some that has perhaps not been given the coverage deserved.
As is the nature of media around scientific “breakthroughs” we are often either left spellbound by or apathetic to the media frenzy as the news saturates our national newspapers, social media timelines and television news channels. But there is also another dimension in play here – namely promising scientific discoveries and initiatives that are flying under the media radar. It is these understated initiatives that also need support and recognition by a Paralysis Community deserving of some much needed wins.
2014 was a landmark year for electrical stimulation, in particular neuromodulation, with news about the four young men making impressive functional and autonomic gains through epidural stimulation via an implanted device.
This led to the launch of the Big Idea campaign by the Reeve Foundation which intends to expand the small study to a larger clinical trial consisting of 36 people. As we write this in 2015, a handful of additional candidates have undertaken the therapy in Louisville, Kentucky and the word on the street is that the results are strikingly consistent with the first four men. We look forward to hearing more as this trial continues.
Continuing the theme of neuromodulation, a paper published in July from Reggie Edgerton’s lab at UCLA remarkably showed that they could elicit identical functional locomotion-like responses from five men using a non-invasive stimulator in combination with an oral drug approved for anxiety disorders. This is incredibly exciting as this non-invasive approach could mean the cost of neuromodulation could be a fraction of the surgical approach used in Louisville, Kentucky whilst also being much easier to navigate through regulatory hurdles to the wider Community. The studies with this non-invasive device continue in order to find the optimal parameters to run a larger multi-centre international clinical trial.
Brain control interfaces
A month ago we saw lots of media attention drawn to a story coming out of UC Irvine whereby a paraplegic walked a few steps using his own brainwaves. The story captured the imagination of the media and public around the world.
The 28-year-old young man was fitted with an EEG cap which relayed an “intent to walk” signal to a computer which in turn triggered electrical impulses (via functional electrical stimulation) to the muscles on his legs in order to contract muscles as steps. Although this is unlikely to be a practical approach in the future due to speed and quality of signal and limitations of functional electrical stimulation to evoke movement it was a great demonstration of being able to decode intent to move from the brain.
Speaking at the Working2Walk symposium in Washington DC, Gregoire Courtine presented the latest update on his own approach to neuromodulation as a neuroprosthetic. He showed footage of spinally injured monkeys being given “spatiotemporal” electricity through computer simulations to excite the motor networks knowing exactly when, how much and the location in the spinal cord to elicit very specific movements. In addition to this very precise “remote control” his lab are developing a wireless platform that would take advantage of a brain implant to decode motor cortex activity, in this case an intent to make specific movements, and use that information to deliver stimulation to the spinal cord to evoke the movement. This combination would be a massive advancement on the fairy simple approach reported last month from UC Irvine.
What about regeneration?
In contrast to the stimulation approaches which are looking to tease more function from the spared spinal cord or to by-pass the injury site there has also been some exciting progress of strategies targeting the repair and regeneration of the injured spinal cord.
At the Spinal Research Network meeting in September there were a number of presentations from UK researchers working on low-level biological studies to understand how the uninjured and injured spinal cord behaves and why the human spinal cord struggles to repair itself after injury.
Excellent presentations from Thanos Didangelos of the Bradbury Lab at Kings College London on using high-throughput proteomics (using computing power to analyse thousands of proteins) to reveal acute and chronic inflammation of the spinal cord and Professor James Fawcett on energising axons to regenerate through the understanding of integrin (signalling pathways) biology.
Yazi Al’joboori from the Ichiyama Lab at Leeds University presented some positive animal data using a combination of a chondroitinase lentivirus and epidural stimulation whilst Jamuna Selvakumaran from Royal Holloway presented on the development of lentiviral vectors as drug delivery systems (part of the CHASE IT initiative) for the central nervous system.
Speaking at Working2Walk, Jan-Eric Ahlfors, CEO of Novagenesis Foundation, presented details of their proprietary autologous neural stem cells programming and regeneration matrix combination. Not only did he present the concept of their technology and some animal (rodent) experimentation but he also showed some interim results and videos from a human clinical trial taking place in Moscow in Russia.
Four chronic spinally injured individuals were transplanted with the reprogrammed cells derived from their own bone marrow placed inside a proprietary regeneration biomatrix. Videos were shown of men being able to move their hips and knees voluntarily and one even stood up with some aid from his hospital bed. Ahlfors also presented charts and electrophysiological exams showing positive changes in muscle activity and sensation. What do we make of all of this? Well, until we see the final peer-reviewed results of the clinical trial we need to take these interim results for what they are – interim – but it’s certainly a group to keep an eye on over the coming years as they look to refine their technology and collaborate with other groups in the field.
Dr Nick Jeffery of Iowa State University spoke at both Working2Walk and the Spinal Research Network meetings about the benefit of using naturally injured dogs as clinical trial patients. Dr Jeffery, originally from the UK is currently two-thirds of the way through a 60-dog clinical trial using a chronic scar busting enzyme called chondroitinase which is seen by many in the field as one of the final steps before moving the enzyme to human clinical trials. We wait eagerly for the results of the clinical trial in the next 12-18 months.
Dr Dalton Dietrich of the Miami Project, also speaking at Working2Walk, announced the first transplant of autologous Schwann cells into the spinal cord of a chronic injury had taken place. The clinical trial will look to establish the safety and efficacy of the schwann cells in promoting the repair of the injured spinal cord. We look forward to hearing more as the trial progresses.
Earlier in the February newsletter we reported on the launch of the Conquer Paralysis Now Incentive Prize which aims to incentivise the field to find a cure for chronic paralysis within the next 10 years. Recently a number of interim prizes have been awarded for novel solutions solving key challenges to repairing the chronic spinal cord. Round 2 of Stage I is now open for submissions offering 12 grants of up to $50,000 across 6 award categories. If you are interested in taking part details can be found here.
A few weeks you may have seen some news covering a very interesting approach to the discovery of spinal injury repair strategies. SCI-VISION is a new Big Data platform developed out of University of California San Francisco which uses “machine learning” and statistics on existing spinal cord injury research data to find new trends and insights for discovery. In this documented case the software sifted through data that had been discarded by research 20 years ago and found that there is a relationship between patients with high blood pressure during their initial surgeries and the long term recovery after spinal injury. Although this in isolation own is a modest finding it is exciting to see that this new approach could very quickly yield many more new discoveries from old studies that have already taken place decades ago as well as the ones underway and to come. We look forward to seeing more discoveries being made from SCI-VISION in the future.
Finally, we reference back to a very important strategy presented by Dr Dalton Dietrich of the Miami Project. Prior to the enrolment of the chronic trial the Miami Project are putting candidates through many months of intensive activity-based rehabilitation programmes much like the ones we provide at neurokinex in order to make sure the body and central nervous system is primed for the schwann cell intervention. This is a very important point as clinical trials for the chronic paralysis community will need a population without secondary complications and with optimal cardiovascular health and musculoskeletal integrity prior to delivering these reparative interventions. At neurokinex, we believe that not only is activity-based rehabilitation important to maximise function and health today but it is also an important primer as reparative strategies of the future approach reality.
The neurokinex team