Spinal cord injury research
Spinal cord injury research seeks new ways to cure or treat
Pathophysiology
Complications from a secondary SCI are a result of a homeostatic imbalance potentially leading to metabolic and hemostatic changes from an inflammatory response. Potential immediate effects of secondary SCI include neuronal injury, neuroinflammation, breakdown of blood-spinal cord barrier (BSCB), ischemic dysfunction, oxidative stress, and daily-life function complications.
Animal models
Animals used as SCI
Limitations of these model experiments are common. For instance,
Epidural cooling saddles, surgically placed over acutely traumatized spinal cord tissue, have been used to evaluate potentially beneficial effects of localized hypothermia, with and without concomitant glucocorticoids.[4][5]
Surgery
Surgery is currently used to provide stability to the injured
In 2014
Neuroprotection
Neuroprotection aims to prevent the harm that occurs from secondary injury.
Hypothermia
One experimental treatment,
Methylprednisolone
Inflammation and glial scar are considered important inhibitory factors to neuroregeneration after SCI. However, aside from methylprednisolone, none of these developments have reached even limited use in the clinical care of human spinal cord injury in the US.[14] Methylprednisolone can be given shortly after the injury but evidence for harmful side effects outweighs that for a benefit.[6] Research is being done into more efficient delivery mechanisms for methylprednisolone that would reduce its harmful effects.[1]
Neuroregeneration
Neuroregeneration aims to reconnect the broken circuits in the spinal cord to allow function to return.[2] One way is to regrow axons, which occurs spontaneously in the peripheral nervous system. However, myelin in the central nervous system contains molecules that impede axonal growth; thus, these factors are a target for therapies to create an environment conducive to growth.[2] One such molecule is Nogo-A, a protein associated with myelin. When this protein is targeted with inhibitory antibodies in animal models, axons grow better and functional recovery is improved.[2]
Stem cells
An ongoing Phase 2 trial in 2016 presented data[20] showing that after 90 days of treatment with oligodendrocyte progenitor cells derived from embryonic stem cells, 4 out of 4 subjects with complete cervical injuries had improved motor levels, with 2 of 4 improving two motor levels (on at least one side, with one patient improving two motor levels on both sides). The trial's original endpoint had been 2/5 patients improving two levels on one side within 6–12 months. All 8 cervical subjects in this Phase 1–2 trial had exhibited improved upper extremity motor scores (UEMS) relative to baseline with no serious adverse side effects, and a 2010 Phase 1 trial in 5 thoracic patients has found no safety issues after 5–6 years of follow-up.
Six-month efficacy data is expected in January 2017; meanwhile, a higher dose is being investigated and the study is now also recruiting patients with incomplete injuries.[21]
In 2022, a team reported the first[22] engineered functional human (motor-)neuronal networks derived from induced pluripotent stem cells (iPSCs) from the patient for implantation to regenerate injured spinal cord that shows success in tests with mice.[23][24]
Embryonic stem cells
Embryonic stem cells (ESCs) are
Neural stem cells
Mesenchymal stem cells
Mesenchymal stem cells do not need to come from fetuses, so avoid difficulties around ethics; they come from tissues including bone marrow, adipose tissue, the umbilical cord.[1] Unlike other types of stem cells, mesenchymal cells do not present the threat of tumor formation or triggering an immune system response.[1] Animal studies with injection of bone marrow stem cells have shown improvement in motor function; however not so in a human trial a year post-injury.[1] More trials are underway.[1] Adipose and umbilical tissue stem cells need further study before human trials can be performed, but two Korean studies were begun to investigate adipose cells in SCI patients.[1]
Olfactory ensheathing cells
Transplantation of tissues such as
Induced pluripotent stem cells
Japanese researchers in 2006 discovered that adding certain transcription factors to cells caused them to become pluripotent and able to differentiate into multiple cell types.[6] This way a patient's own tissues could be used, theoretically because of a reduced chance of transplant rejection.[6]
Engineering approaches
Recent approaches have used various engineering techniques to improve spinal cord injury repair. Use of
Hydrogels
Bionanoengineered scaffolds
In November 2021, a novel therapy for spinal cord injury was reported – an injectable gel of nanofibers that mimic the matrix around cells and contain molecules that were engineered to wiggle. These moving molecules connect with receptors of cells, causing repair signals inside – in particular, leading to relatively higher vascular growth, axonal regeneration, myelination, survival of motor neurons, reduced gliosis, and functional recovery – enabling paralyzed mice to walk again.[34][35][36]
Exoskeletons
The technology for creating powered exoskeletons, wearable machinery to assist with walking movements, is currently making significant advances. There are products available, such as the Ekso, which allows individuals with up to a C7 complete (or any level of incomplete) spinal injury to stand upright and make technologically assisted steps.[37] The initial purpose for this technology is for functional based rehabilitation, but as the technology develops, so will its uses.[37]
Functional electrical stimulation (FES) uses coordinated electric shocks to muscles to cause them to contract in a walking pattern.[38] While it can strengthen muscles, a significant downside for the users of FES is that their muscles tire after a short time and distance.[38] One research direction combines FES with exoskeletons to minimize the downsides of both technologies, supporting the person's joints and using the muscles to reduce the power needed from the machine, and thus its weight.[38] A research team at the McKelvey School of Engineering at Washington University in St. Louis, led by assistant professor of biomedical engineering Ismael Seáñez, is launching a clinical trial of electrical spinal cord stimulation for helping restore movement in movement-impaired or paralyzed patients.[39]
Brain–computer interface
Recent research shows that combining brain–computer interface and functional electrical stimulation can restore voluntary control of paralyzed muscles. A study with monkeys showed that it is possible to directly use commands from the brain, bypassing the spinal cord and enable limited hand control and function.[40]
Spinal cord implants
Spinal cord implants, such as e-dura implants, designed for implantation on the surface of the spinal cord, are being studied for paralysis following a spinal cord injury.[41]
E-dura implants are designed using methods of soft neurotechnology, in which electrodes and a microfluidic delivery system are distributed along the spinal implant.[42] Chemical stimulation of the spinal cord is administered through the microfluidic channel of the e-dura. The e-dura implants, unlike previous surface implants, closely mimic the physical properties of living tissue and can deliver electric impulses and pharmacological substances simultaneously. Artificial dura mater was constructed through the utilization of PDMS and gelatin hydrogel.[42] The hydrogel simulates spinal tissue and a silicone membrane simulates the dura mater. These properties allow the e-dura implants to sustain long-term application to the spinal cord and brain without leading to inflammation, scar tissue buildup, and rejection normally caused by surface implants rubbing against nerve tissue.
In 2018 two distinct research teams from Minnesota's Mayo Clinic and Kentucky's University of Louisville managed to restore some mobility to patients suffering from paraplegia with an electronic spinal cord stimulator. The theory behind the new spinal cord stimulator is that in certain cases of spinal cord injury the spinal nerves between the brain and the legs are still alive, but just dormant.[43] On 1 November 2018 a third distinct research team from the University of Lausanne published similar results with a similar stimulation technique in the journal Nature.[44] [45] In 2022, researchers demonstrated a spinal cord stimulator that enabled patients with spinal cord injury to walk again via epidural electrical stimulation (EES) with substantial neurorehabilitation-progress during the first day.[46][47] In a study published in May 2023 in the journal Nature, researchers in Switzerland described implants which allowed a 40-year old man, paralyzed from the hips down for 12 years, to stand, walk and ascend a steep ramp with only the assistance of a walker. More than a year after the implant was inserted, he has retained these abilities and was walking with crutches even when the implant was switched off.[48]
References
- ^ S2CID 23121381.
- ^ PMID 26343846.
- PMID 27147970.
- PMID 11052347.
- PMID 1006512.
- ^ PMID 26124844.
- ^ Bigelow & Medzon 2011, pp. 176–77.
- TheGuardian.com. 20 October 2014.
- ^ "Therapeutic Hypothermia: eMedicine Clinical Procedures". Retrieved 21 February 2011.
- ^ "Hypothermia". Retrieved 21 February 2011.
- S2CID 12799582.
- S2CID 39978864.
- PMID 15658119.
- PMID 21080129.
- ^ PMID 26439026.
- ^ Abraham S (March 2008). "Autologous Stem Cell Injections for Spinal Cord Injury – A multicentric Study with 6 month follow up of 108 patients". 7th Annual Meeting of Japanese Society of Regenerative Medicine, Nagoya, Japan.[verification needed]
- ^ R Ravikumar, S Narayanan and S Abraham (November 2007). "Autologous stem cells for spinal cord injury". Regenerative Medicine. 2 (6): 53–61.[verification needed]
- ^ Abraham S (June 2007). "Autologous Bone Marrow Mononuclear Cells for spinal cord injury: A case report". Cytotherapy. 9 (1).[verification needed]
- ^ Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, ed. (2013). Spinal Cord Injury: Hope Through Research. Bethesda, MD: National Institutes of Health. Archived from the original on 19 November 2015.
- ^ Wirth, Edward (14 September 2016). "Initial Clinical Trials of hESC-Derived Oligodendrocyte Progenitor Cells in Subacute Spinal Cord Injury" (PDF). ISCoS Meeting presentation. Asterias Biotherapeutics. Retrieved 14 September 2016.
- ^ "Asterias Biotherapeutics Announces Positive Efficacy Data in Patients with Complete Cervical Spinal Cord Injuries Treated with AST-OPC1". asteriasbiotherapeutics.com. Retrieved 15 September 2016.
- Tel-Aviv University. Retrieved 10 March 2022.
- ^ "Engineered spinal cord implants restore movement to paralysed mice". Physics World. 23 February 2022. Retrieved 10 March 2022.
- S2CID 246633147.
- S2CID 206516299.
- ^ "CTG Labs - NCBI". 16 June 2015.
- S2CID 30934447.
- S2CID 35220044.
- PMID 25815131.
- S2CID 10199210.
- PMID 18385339.
- PMID 21303267.
- PMID 21636129.
- ^ "Therapy used on mice may transform spinal injury treatments, say scientists". The Guardian. 11 November 2021. Retrieved 11 December 2021.
- ^ University. "'Dancing molecules' successfully repair severe spinal cord injuries in mice". Northwestern University. Retrieved 11 December 2021.
- PMID 34762454.
- ^ a b "Ekso Bionics - Pioneers in Wearable Bionic Exoskeleton Suits Since 2005". 26 July 2021.
- ^ PMID 22773254.
- ^ "New research focuses on restoring movement after spinal cord injury". News-Medical.net. 6 September 2022. Retrieved 7 September 2022.
- PMID 22522928.
- ^ Paddock, Catharine (2015). Soft spinal implants show promise as long-term solution paralysis. Medical News Today. Retrieved 03/09/2015.
- ^ S2CID 1941485.
- ^
"Spinal implant helps paralyzed patients walk". Deutsche Welle. 24 September 2018. Retrieved 4 October 2018.
Spinal cord stimulators and intense physical therapy are helping paraplegic patients relearn how to walk. Spinal cord stimulators can potentially help "wake up" dormant nerves.
- ^
Chen, Angus (31 October 2018). "Spinal Stimulator Implant Gives Paralytic Patients a Chance to Regain Movement". Scientific American. Springer Nature. Retrieved 1 November 2018.
A new therapy that amplifies nerve impulses may also help the body heal
- ^
Wagner, Fabien B. (1 November 2018). "Targeted neurotechnology restores walking in humans with spinal cord injury". S2CID 53148162.
- ^ "Paralysed man with severed spine walks thanks to implant". BBC News. 7 February 2022. Retrieved 10 March 2022.
- S2CID 246651655.
- ^ Whang, Oliver (24 May 2023). "Brain Implants Allow Paralyzed Man to Walk Using His Thoughts". The New York Times. Archived from the original on 26 July 2023.
Bibliography
- Bigelow, S.; Medzon, R. (16 June 2011). "Injuries of the spine: Nerve". In Legome, E.; Shockley, L.W. (eds.). Trauma: A Comprehensive Emergency Medicine Approach. Cambridge University Press. ISBN 978-1-139-50072-2.