Can experiments in nonhuman primates expedite the translation of treatments for spinal cord injury in humans?

Abstract

Progress continues in the development of reparative interventions to enhance recovery after experimental spinal cord injury (SCI). Here we discuss to what extent rodent models of SCI have limitations for ensuring the efficacy and safety of treatments for humans, and under what circumstances it would be advantageous or necessary to test treatments in nonhuman primates before clinical trials. We discuss crucial differences in the organization of the motor systems and behaviors among rodents, nonhuman primates and humans, and argue that studies in nonhuman primates are critical for the translation of some potential interventions to treat SCI in humans.Traumatic SCI has long-term health, economic and social consequences worldwide 1,2 , giving a sense of the urgency to the development of ways to treat it. Treatments that lead to at least partial functional recovery after SCI can substantially improve the quality of life of affected individuals. Consequently, there is considerable need to take to the clinic those interventions that have shown effectiveness in promoting functional improvement in laboratory animals.Progress continues in the identification of interventions that augment plasticity after injury by promoting axonal regeneration and sprouting in rodents [3][4][5][6] . Some of these treatments may be efficacious in patients with SCI, and have or are entering phase 1 clinical trials. Important differences exist, however, between the nervous systems of rodents and humans,

Pharmacological comparison of a nonhuman primate and a rat model of oxaliplatin‐induced neuropathic cold hypersensitivity

“…Nonhuman primates (NHP) are a favored species in neuroscience research because of their complex neuroanatomy, compared to that of rodents, and their expression of clinically relevant symptoms in neurological disorders such as in Parkinson's disease (Courtine et al. 2007; Capitanio and Emborg 2008). …”

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

“…On the other hand, if the potential risk of a proposed therapy is higher (e.g., surgical manipulation of the lesion site and/or surrounding spared tissue in SCI), evidence of greater potential efficacy is necessary. It is for the latter studies in particular that a primate model of SCI can be beneficial [2].…”

“…However, whether or not results obtained from studies in these models can be extrapolated to primates, including humans, depends on the specific motor task and the similarities in the anatomical and functional organization of the sensorimotor systems between lower and higher order mammals [2,8,9]. A good understanding of the comparative function of the sensorimotor system is critical to determining these limitations and understanding the relevance of the information that the different animal models provide.…”

“…Function: Some important axon systems have different functional roles in primates and rodents. For example, the corticospinal tract is critical for fine motor control in humans and nonhuman primates, but less critical in rats [2,13,15]. On the other hand, the rubrospinal tract is important for forelimb movement in rats, but is vestigial in humans [16].…”

“…In addition, this model has been instrumental in developing and testing translational treatment methodologies, including the observation that treatment methods used in rodents [19][20][21][22][23][24][25][26] were problematic in primates [27]. We believe that primates should be used sparingly and only when models in less developed species are inadequate for addressing important mechanistic or translational questions; there is a clear and necessary role for nonhuman primate studies under these conditions [2,15].…”