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Drug and cell therapies for SCI

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By:

Ana-Maria Oproescu and Victoria McCann

This is a summary of a literature review which combines the findings of many individual studies about drug and cell therapies for SCI and discusses the major developments and challenges in these areas of research. The review was published by researchers in the Department of Biomedical Engineering at the Cleveland Clinic and the Department of Orthopedics at the University of British Columbia, with ICORD researcher Dr. Brian Kwon.

Click here to access the original article.

Contextual Information

For those living with SCI, treatment strategies are complicated by secondary injury to the nervous system. After the initial trauma to nervous tissue, damaged cells from the original site may lead to further damage by contributing to the formation of scars and swelling in the nervous system. This is given the term “secondary damage’ and includes other events such as demyelination (damage to a nerve’s protective covering), improper blood supply to various parts of the body, and damage to cell membranes and genetic information.

What are some of the current approaches to rehabilitation and therapy for people with SCI?

The authors review two different therapeutic approaches: neuroprotective and neuroregenerative. Neuroprotective strategies, such as drug-based therapies, focus on protecting the body from further injury caused by the original SCI. Neuroregenerative therapies, on the other hand, attempt to recover lost function caused by the SCI, and include cell-based and tissue-engineering approaches. While neuroprotective therapies may only be done within a limited time frame, neuroregenerative therapies may be done throughout one’s life. The authors identified the challenges and potential of several treatments.

Challenges Progress
Drug Delivery (Neuroprotective)
  • Maintaining an appropriate drug-dosage at the site of injury within the body is an important barrier in drug-based therapies.
  • Humans often have lower tolerance to similar dosages that have been proven effective in animal models when administered through the circulatory system.
  • New vehicles have been identified as ways to pass from the blood vessels to the cerebrospinal fluid (blood-spinal cord barrier, BSCB) providing new, non-invasive ways for drugs to access the injured site from the blood.
  • These nanoparticle-mediated drug delivery methods are a solution to the challenges described above.
  • Many clinical trials are underway to test the effects of various drug therapies with positive results relating to pain reduction, reduced muscle spasms, functional recovery, and neurological recovery.
Cell-Based Therapy (Neuroregenerative)
  • SCI creates an unfavourable environment for transplanted tissues and cells to integrate.
  • The rejection of transplanted tissues, and the formation of tumors are all concerns in this area of research.
  • Cell transplantation has become one of the most important areas of clinical research in neuroregeneration.
  • Transplanting tissues (such as nerve-encasing Schwann cells, fetal tissues, and olfactory-ensheathing cells) creates a better environment in the SCI for neuro-regeneration.
  • Researchers are able to genetically modify cells that can promote nerve regeneration when transplanted.
  • Some stem cells are less cancer-causing than others. Neural stem cells have been shown effective in treating patients with stroke, Parkinson’s, and cerebral palsy, and are less cancer-causing than embryonic stem cells (cells derived during early human development).
Tissue Engineering (Neuroregenerative)
  • Although the spinal cord does have some inherent ability to repair itself, this is made difficult after SCI because of the hostile cellular environment created by the injury.
  • The biomaterials used must meet many criteria: they must not compress the surrounding spinal tissue, they must not be harmful to surrounding tissue, and lastly they must degrade at a proper rate in coordination with the growth of axons and tissues.
  • Numerous biomaterials (such as hyaluronic acid and collagen-based grids) have been tested to rebuild tissue that has been damaged by SCI.
  • Natural compounds are more effective at supporting cells than synthetic compounds.

What could this mean for the future of SCI treatment?

The authors found that considering the dynamic nature of SCI symptoms, it is important that treatments and therapies take a combined approach. That is to say, the best results will likely be observed when both neuro-protection and neuro-regeneration are targeted within a single treatment.

A common issue with SCI research is that while results may appear promising in a lab setting, they fail to translate to people living with SCI. This review suggests that by establishing certain research guidelines to be met when planning a new therapy, researchers will ultimately be able to reduce the amount of time and effort spent on failed clinical trials. The authors write that more thorough testing procedures such as the use of multiple animal models, different injury models, and more effective drug delivery would prevent unfavorable results from discouraging researchers, patients, and community alike.

The authors are optimistic that one day targeted approaches will be available not only to promote injury repair through treatment, but also to facilitate self-repair of damage related to SCI.