”Unease, anxiety, tension, stress, worry – all forms of fear – are caused by too much future, and not enough presence. Guilt, regret, resentment, grievances, sadness, bitterness, and all forms of nonforgiveness are caused by too much past, and not enough presence.” ― Eckhart Tolle
”Life can be found only in the present moment. The past is gone, the future is not yet here, and if we do not go back to ourselves in the present moment, we cannot be in touch with life.” ― Thich Nhat Hanh
Learning mindfulness or focusing on being and living in the now, is often said to be the basis for positive mental health. Experience what is in your current world (the fact that you are safe, warm, and have food), instead of allowing your mind to wander (from what is in front of your eyes or in your senses) to what could happen tomorrow (worry or hope) or what has occurred in the past (injury, regret, and pain). Planning and working on developing the best health, love, friendships, spiritual and emotional growth and financial security instead of continually focusing on what is missing, lost, or what no longer exists, and what the future holds in “fixing” our disability is how we can create joy and contentment in what is available to us NOW.
Keeping this in mind, we can live healthily in the moment, while being aware of what may be available to improve our health in the future.
Photo Credit: Lawrence Ream
Model: Alexandra Santibanez on PushLivingPhotos
While there is no cure for spinal cord injury yet, truly remarkable gains are being made in the area of research and technology and they cannot be ignored.
We have tried to compile the most promising gains that you can follow and support.
The focus of current research is to improve our understanding of the following principles of spinal cord repair:
- Neuroprotection–protecting surviving nerve cells from further damage
- Regeneration–stimulating the regrowth of axons and targeting their connections appropriately
- Cell replacement–replacing damaged nerve or glial cells
- Retraining CNS circuits and plasticity to restore body functions.
Injury to the spinal cord is complex. To repair this injury, researchers have to take into account different types of damage occurring during and after the injury. As the molecular and cellular environment of the spinal cord changes constantly from the time of injury to several months later, a combination of therapies may have to be provided to address specific types of damage at different stages of the injury.
Here is a look at what is on the horizon, who is making it happen, who will benefit, and what are the possible timelines?
1. Gene therapy: Researchers at King’s College London, Regeneration Group, The Wolfson Centre for Age-Related Diseases, Institute of Psychiatry, Psychology and Neuroscience (IoPPN) have published their preclinical research on gene therapy for tetraplegics. Their novel gene therapy provides an experimental tool to study the of extracellular matrix digestion as well as an encouraging step towards generating a safer chondroitinase gene therapy strategy. The long-term administration of this therapy increases neuroplasticity and recovery of descending motor control. The researchers propose that this gene therapy would develop further into clinical application for treatment of spinal cord injury. The researchers assessed the efficacy of a novel dual lentiviral immune-evasive doxycycline-inducible ChABC (dox-i-ChABC) vector system. In this system, ChABC gene expression is regulated via the widely clinically-available broad-spectrum antibiotic doxycycline (Dox). As a majority of spinal injured individuals are injured at the cervical level (National Spinal Cord Statistical Centre, 2017), a top priority for improving independence and quality of life is recovery of hand and digit function (Anderson, 2004), the researchers investigated the effect of dox-i-ChABC treatment following a clinically relevant cervical spinal contusion injury model in adult rats. This model closely mimics the pathology and progression of spinal cord injury found clinically and affects functions of the upper limb and hand. They could demonstrate the effective regulation of ChABC delivery following injury, where doxycycline administration and removal controls ChABC gene expression. With the help of the tool, they could switch on ChABC transiently or maintain delivery long-term following injury and demonstrate task-specific therapeutic temporal dependence. For example, short-term dox-i-ChABC treatment was sufficient to mediate improvements in a task of sensorimotor ability correlating with increased ascending sensory transmission and sustained dox-i-ChABC treatment conferred additional benefit in a measure of skilled hand function. This indicates anatomical evidence of neuroplasticity of the descending motor pathways. These researchers are not yet recruiting for human trials.
2. Stem cell injection: Asterias Biotherapeutics is performing human stem cell research trial in spinal cord injury (SCI) since 2012. As part of their study, volunteers are injected with 20 million embryonic stem cells. Four of the six people with SCI treated with stem cells have recovered two or more motor levels at least on once side.
3. The Miami Project has several ongoing clinical trials and clinical studies for people with acute and chronic SCI. The trials are testing the safety and efficacy of neuroprotective, reparative, or modulatory interventions. These include treatment with autologous schwann cells, HuCNS-SC ®Stem cells and role of hypothermia in the management of acute SCI. The Miami Project launched their Schwann Cell clinical trial for chronic spinal cord injury patients in February 2015. The transplanted cells are autologous (coming from the patient himself). Latest status (January 2018): The Schwann cell clinical trial completed its phase 1 (to check safety) and showed that the cells were safe. The Miami Project is now carrying out further studies combining the Schwann cells transplantation with various other therapeutic strategies such as intensive physical rehabilitation. (Currently recruiting.) Further studies are also in preparation and might involve the combination of Schwann cells with, respectively, growth factors, antibodies and cell-support matrices. The study is currently recruiting patients with a chronic injury (at least one-year post injury, complete or incomplete C5-T12 injury, 18-65 years old). For details and enrollment see here: NCT02354625
4. Reeve-Irvine Research Center, University of California: Oswald Steward, Ph.D., is the UC Irvine School of Medicine’s senior associate dean for research and director of the Reeve-Irvine Research Center. His research in acute SCI showed that permanent damage can be overcome after the deletion of an enzyme called PTEN, which controls a molecular pathway regulating cell growth. PTEN activity is low during early development, allowing cell proliferation. PTEN subsequently turns on, inhibiting this pathway and precluding any ability to regenerate. PTEN is an enzyme which acts as a brake when axons attempt to regenerate after injury. PTEN may hold the secret cure to SCI recovery.Two years later, a UCI team found that fibrin injected into rats that had spinal cord injuries filled the holes at the injury site, giving axons a framework in which to reconnect and facilitate recovery. Per Stewart, professor of anatomy & neurobiology and director of the Reeve-Irvine Research Center, of the current findings. “Paralysis and loss of function from spinal cord injury has been considered irreversible, but our discovery points the way toward a potential therapy to induce regeneration of nerve connections.” Cure Medical’s founder, Bob Yant, expressed his excitement at the results as he is a quadriplegic himself. “This is the first study to show recovery of function following PTEN inhibition and treatment at the injury site. The animals make a 95% recovery to normal. This is the best recovery in the history of spinal cord injury research,” said Yant. Cure Medical is committed to using 10% of our net income to find a cure for SCI and CNS disorders. Funding research like this shows progress is being made. When will a cure for SCI and CSN disorders be found? We don’t know, but we will work to keep innovative research moving forward.”
Photo Credit:Bob Yant, Founder, Cure Medical
Click here for more information about the medical research programs that Cure Medical supports. You can find out about Cure Medical’s funding paralysis research here.
5. Neuralstem Inc. – Neural Stem Cells: A clinical trial sponsored by the biotech company Neuralstem was started in the USA in October 2014. Its primary objective was to confirm the safety of their neural stem cells (NSI-566), on chronic SCI patients. Four patients have been treated. In October 2015, it was reported that the stem cells implantation had been safe and well tolerated. In January 2018, the trial had a go -ahead to recruit more patients as per Dr Ciacci. The University of California San Diego (UCSD) has begun recruiting four more participants with complete (Asia A) chronic cervical injury (C5-C7, 1 to 2-year post injury), to continue the trial under an amended protocol. The trial is being conducted at the university’s Sanford Stem Cell Clinical Center. Researchers recommend that participants in the trial live within a 500-mile radius of San Diego, due to the intensive, 60-month follow-up schedule. For more information on the Phase I Chronic SCI study, contact Ciacci’s Research Group at
(619) 471-3698, nksidhu@ucsd.edu.
6. Nose Cells and Nerve Graft: In October 2014, a paralyzed Polish man was reported to have gained recovery after some of his nose nerve cells (these were actually taken from the olfactory bulb deep in his brain) were transplanted into his spinal cord and some peripheral nerve tissue from the patient’s ankle was grafted to serve as a bridge over the lesion. He went from complete paraplegia to incomplete (Asia A to Asia C) and has regained considerable functions. Here is a link to the published data. This study was pioneered by the late Dr. Raisman (deceased 2016). As of January 2018, chronic SCI patients are still being recruited for a new clinical trial taking place in Poland (Dr. Tobakow). Only patients with a transected/severed spinal cord can apply for the trial. The cord must be clear-cut, for example by a knife, not confused. Also, the candidates for this clinical are required to spend several years in Poland as the procedure will be preceded and followed by an intensive and lengthy rehabilitation process. More info regarding enrollment is available here. Moreover, another clinical trial is in preparation, in the UK, following a slightly different protocol (the source of the olfactory cells might be different) and other patient selection criteria. There is no public update available regarding this UK trial plan but it might involve acute injuries rather than chronic cases.
7. Umbilical Cord Blood Stem Cells and combinations: Dr. Wise Young published results of phase II trials. In 2014, Dr. Wise Young, Rutgers University and SCINetChina, presented some preliminary information from the Umbilical Cord Blood & Lithium Phase II clinical trial that had taken place in China. 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 the aid of a walker whilst in rehabilitation. See abstract of the publication here. A lot of questions remain as to the extent of “functional” recovery obtained (is it functional even though the motor scores of patients have not improved, meaning that they cannot contract any muscle on order?). Currently Dr. Wise Young is raising funds to carry out a similar clinical trial in the USA, Phase IIb (aiming to prove efficacy) which will consist of three groups of nine, ASIA A, C5-T10 patients. The first group will get umbilical cord blood stem cell injections plus six weeks of oral lithium plus intensive rehab. The second group will get umbilical cord blood stem cells plus intensive rehab. Group three will get intensive rehab only. A list of Questions and Answers regarding the upcoming clinical trial is available here. Information regarding the intensive walking program included in the study is published here. This study is in preparation and is not recruiting patients yet.ch, therapies, treatments, 2018
8. Bone Marrow Stem Cells Intrathecal Injection- Dr. Vaquero Phase II clinical trial (Spain) – Phase II trial completed. Dr Vaquero (M.D. Puerta de Hierro University Hospital, Spain) has been studying the impact of the autologous (from the patient himself) bone-marrow mesenchymal stem-cells intrathecal injection (in the subarachnoid space). A phase II of the trial has been carried out on incomplete spinal cord injury patients. According to Vaquero, (this) cell therapy helps, above all, “people who have a healthy nervous system, but does not guarantee success in a person with a complete spinal cord injury.” For patients with an incomplete spinal cord injury, this therapy can significantly improve sphincter control. In fact, Dr. Vaquero has presented several cases in which people affected by an (incomplete) spinal cord injury can more effectively control incontinence and effectively improve bladder emptying. That cell therapy also improves spasticity and sexual function […]. Source (in Spanish- article June 2017). More scientific details in the 2016 publication (complete SCI) and 2017 publication (results for incomplete SCI).Cure Spinal Cord Injury Research, therapies, treatments, 2018
9. Neuroplast (The Netherlands) – Autologous Bone Marrow-derived Stem-Cells – Clinical trial in preparation for both chronic and acute SCI. Neuroplast is an independent company founded in 2013 in the Science Society of Brightlands Maastricht Health Campus (brightlands.com), The Netherlands. “A pre-clinical study showed that Neuro-Cells (Neuroplast proprietary cells that are derived from the patient’s own bone marrow) did significantly improve both locomotor functions and survival in those spinal cord-lesioned rats as compared to rats treated with a placebo“. Neuroplast is preparing two studies that are expected to take place in Europe. The studies involve a transplantation of Neuro-Cells that are said to have a positive effect both in terms of neuro-protection and neuro-plasticity and are expected to contribute to the level of functional recovery for patients both at an acute and chronic stage of the lesion. As of 2018, Neuroblast is now conducting the regulatory safety study and building partnerships with various European centers that will be involved in the implementation of the trials. Europe. There will be two studies:
– A phase I trial for chronic spinal cord injury patients. It is expected to start in 2018 and should enroll ten patients with an SCI <2 years, Asia A, Asia B or Asia C (complete or incomplete SCI). The trial will take place in The Netherlands. The safety check will last three months and the patients will be followed up for one year after that, in order to check the effectiveness of the treatment.
– A phase II/III trial for which 81 patients with a sub–acute SCI will be recruited. The study will last two years for the patients and will take place in various European countries including The Netherlands.
Both trials are in preparation. Patients are not yet being recruited. It is expected that the first five patients with chronic spinal cord injury will be recruited soon.
10.BioArctic – SC0806 (biodegradable device+ FGF1): clinical trials approved and recruiting patients in Sweden and Slovenia. SC0806 is a combination of a biodegradable medical device and a drug substance (FGF1) designed to support nerve regeneration across the injured area in the spinal cord. The therapy is developed by BioArctic AB, a Swedish research-based biopharma company. BioArctic has received regulatory approval in Estonia for a clinical study in patients with Complete Spinal Cord Injury. The product candidate is currently in an ongoing Phase 1/2 clinical trial. The first patient was treated in 2016 at Karolinska University Hospital, Sweden. The Estonian patients will undergo treatment with SC0806 at the Karolinska University Hospital in Stockholm, Sweden, followed by an 18-months training period in the study to enhance the patients’ motor ability in the paralyzed part of the body. The rehabilitation will initially take place in Sweden and will then continue in Estonia.
11.Dr. Bresnahan, UCSF’s research focuses on understanding the biological underpinnings of neurotrauma, particularly spinal cord injury, with the goal of improving recovery for individuals who suffer damage to the nervous system. Her laboratory has developed a number of models to study cellular systems and behavioral changes that occur as a consequence of injury.
12. Dr. James Fawcett’s team, University of Cambridge is developing a microchannel interface prosthesis which allows permanent extracellular recording from axons. This is being developed for control of bladder function and for controlling prosthetic limbs.
13. Dr. Zhigang He, Harvard University’s recent studies have led to the development of novel and effective genetic methods (deletion of PTEN and/or SOCS3) for re-activating neuronal regenerative capacity and thereby allowing for robust regenerative growth after injury, representing a major achievement in the first step of the neural repair.
14. Dr. McMahon’s team, Kings College, London: Dr. McMahon has shown that degrading one component of the post-injury scar enables regeneration of damaged central nerves and restores some sensory and movement behaviors. His research areas include behavioral, electrophysiological and anatomical studies of somatosensory systems, particularly pain; and spinal cord injury. Dr. McMahon’s team is currently exploring a number of approaches to repair spinal cord injuries. They have shown, in preclinical models, that one form of spinal injury – avulsion of nerve roots – can be treated with neurotrophic factors. These factors are insufficient to repair injures of the spinal cord itself. An important reason seems to be the inhibitory nature of the glial scar that forms at the site of central nervous system lesions.
15. Jerry Silver, Case Western Reserve University. Although highly controversial from its inception, the Silver lab was one of the very first to suggest that overtly growth-repulsive environments, whose function was to actively turn axons away from improper trajectories during embryogenesis, might reappear in the injured CNS and block the attempt of severed axons to re-grow. The lab’s research strategy shows clearly, for the first time, that long distance regeneration, with appropriate re-formation of functional connections, can be achieved in the adult after catastrophic spinal cord injury providing real hope that we are now entering an era where strategies for providing functional benefit in models of spinal cord injury are sufficiently robust that there should be optimism for translational success.
16. Mark Tuszynski, UC San Diego: He uses the genes of nerve growth factors to stimulate regeneration in the injured spinal cord. Dr. Tuszynski’s Spinal Cord Injury (SCI) Hypothesis is that combinatorial therapeutic strategies can enhance axonal plasticity and regeneration after acute and chronic SCI.The failure of the spinal cord to regenerate after injury is caused by (1) lack of production of growth-promoting substances such as growth factors in the injury site, (2) lack of permissive bridges for axon growth within injury sites, (3) deficiency of strong signals for the injured cell to re-enter an active growth state, and (4) blockade of growth by inhibitors in the injured region. This research program tests the ability of cells and growth factors to promote regeneration after SCI. Tested cells include stem cells, autologous bone marrow cells, Schwann cells, and fibroblasts. The Tuszynski group is examining both acute and chronic models of SCI.
Summary
People who live with paralysis can look forward to exciting times. Although cure for paralysis is not yet available, there are several promising clinical trials underway which may lead to a nerve regeneration and recovery. These research trials include novel gene therapy, stem cell therapy, autologous bone marrow cell therapy, biodegradable devices and prosthetics. More benefactors like Bob Yant can help speed these trials to find an early cure for all those living with paralysis.