Immune-based therapies for Central Nervous System trauma

Jonathan B. Marder, PhD; Gustavo Auerbach, DMD; Linda Jones, PT; Irit Shefer; David Snyder, PhD

INTRODUCTION:
Traumatic damage to the central nervous system (CNS) leads a wave of cell
degeneration causing loss of neurological function. The damage is permanent
because the CNS has an extremely limited capacity for nerve regeneration.
Other tissues, including peripheral nerves, have active repair mechanisms
in which the immune system plays a central role clearing debris and toxic
elements, and supporting new growth. While the immune system does respond
to CNS damage, the activity is suppressed by the "immune privilege".
However, controlled boosting of the immune response has therapeutic
potential.

METHODS:
Several methods have been developed for immune therapies to treat CNS
trauma. These include a cell therapy using autologous skin-coincubated
macrophages, vaccines that induce a neuroprotective effect that attenuates
post-traumatic damage, and an immunomodulators (PN277) that improve the
spontaneous immune response.

RESULTS:
Incubated macrophages were shown to induce nerve recovery in several
preclinical models including rat optic nerve transection, rat spinal cord
transection and rat spinal contusion. The therapy was adapted for clinical
use in a Phase I clinical trial that provided prelimary evidence of safety
and efficacy. Neuroprotective vaccination was tested in animal models of
white and gray injury, with different antigens providing protection in
different models depending on their tissue specificities. PN277
immunomodulator was found effective in a wide spectrum of animal models for
neurotrauma and neurodegenerative disease, notably stroke and optic nerve
trauma.

CONCLUSIONS:
Immune-based cell therapies, neuroprotective vaccines and immune modulators
have significant potential in the treatment of many neurological disorders,
including trauma to the brain and spinal cord.

KEYWORDS: Spinal cord injury, stroke, neuroprotective immunity

OBJECTIVES: The objective is to provide novel therapies for neurological
disorders for which there are no treatments available.