Demonstrating efficacy in preclinical studies of cellular therapies for spinal cord injury — How much is enough?

Central Nervous System

“…Some of the important characteristics of an experimental treatment that ideally should be established before human study [38,101,191] include: l therapeutic target or mechanism of action (though this often remains speculative to some extent) l expected side effects or adverse events (i.e., safety in animals, generally in at least two species) l optimal therapeutic formulation and dose or optimal cell type and number of cells l optimal route of administration In the following section, we will discuss key challenges faced by drug and cell therapy strategies used in neuroprotection and neuroregeneration in the CNS and highlight strategies being investigated in preclinical research to address these challenges.…”

“…To provide some objective guidance to weigh the possible risks and benefits for a human study, an initial set of SCI clinical trial guidelines was developed and published by an international panel of scientists and clinicians [96][97][98][99] as well as an open document for the public and healthcare professionals [100]. They recommend that treatments be tested in a number of different SCI models/ species and replicated in independent laboratories before moving into clinical trials [101].…”

Effect of Bone Marrow-derived Mesenchymal Stem Cells on Changes of Serum Levels of TNF-α and Locomotor Function after Spinal Cord Injury in Mice

“…The role of TNF-α is extended from the immune system to neuro-inflammatory in the nervous system (Leung and Cahill, 2010). Therefore, there is a need to improve functional recovery of spinal cord after injury including control of inflammation (Dyck et al, 2015), rescue of neural tissue (Kwon et al, 2013) stimulation of axonal regeneration by modulation of the lesioned environment (Eftekharpour et al, 2008) or promotion of remyelination (Gauthier et al, 2013).…”

Developing a spinal cord injury research strategy using a structured process of evidence review and stakeholder dialogue. Part I: rapid review of SCI prioritisation literature

“…12 There are also multiple methods for deciding on priorities as outlined by Viergever et al, 12 which can be classified broadly into consensus-based approaches (driven by stakeholder input), metrics-based approaches (for example, the Delphi technique) and combination approaches (for example, prioritisation followed by discussion using a nominal group approach). Two recent examples of SCI research prioritisation are Guest et al's 14 description of the prioritisation process followed by the North American Clinical Trials Network, which is based on earlier work by Kwon et al 15,16 who developed a scoring system for grading pre-clinical literature on neuroprotective treatments for acute SCI.…”

“…12 There are also multiple methods for deciding on priorities as outlined by Viergever et al, 12 which can be classified broadly into consensus-based approaches (driven by stakeholder input), metrics-based approaches (for example, the Delphi technique) and combination approaches (for example, prioritisation followed by discussion using a nominal group approach). Two recent examples of SCI research prioritisation are Guest et al's 14 description of the prioritisation process followed by the North American Clinical Trials Network, which is based on earlier work by Kwon et al 15,16 who developed a scoring system for grading pre-clinical literature on neuroprotective treatments for acute SCI.The purpose of this review was to gain an overview of the volume, nature and findings of studies that aimed to identify priorities for SCI research. This was undertaken as part of a structured process of evidence synthesis (rapid review) and stakeholder consultation (expert opinion) to develop a regional (Australia and New Zealand) SCI research strategy.…”