Biology Reference
In-Depth Information
1. INTRODUCTION
Despite preclinical findings—the first promising study was published
more than 30 years ago (
Richardson, McGuinness, & Aguayo, 1980
)—
clearly demonstrating the capacity of the injured mammalian spinal cord
to regenerate, not a single experimental treatment translated into the clinical
setting. A recent review pointed this out in a rather provocative title: “Cen-
tral nervous system (CNS) regeneration does not occur” (
Illis, 2012
). Illis
states “the long history of research in regeneration in the CNS centered
on the site of the lesion has proved to be sterile. After a century of such re-
search the focus should move away from the site of the lesion to the intact
CNS where there is real promise of improvement of function.” Of course, it
is considered easier to achieve structural rearrangements rostral and caudal to
the SCI site in order to compensate for lost function after irreversible tran-
section of long descending and ascending fiber tracts. However, such a strat-
egy will be helpful only in incomplete spinal cord injury (SCI), where a
relevant proportion of spared axons still cross the lesion site. However,
the vast majority of severely injured sensory-motor complete patients will
not gain clinically meaningful functional benefits from such neural
rearrangements beyond the lesion site. For these patients, separate from ef-
forts to compensate lost function with neuroprosthetic devices (
Rupp &
Gerner, 2007
), the sole neurobiological option is to reconnect the injured
spinal cord appropriately.
Although results in terms of therapeutic efficacy are discouraging, we can
learn tremendously from existing preclinical and clinical research in order
to implement this knowledge into new intelligent approaches. In this
review, four different bench to bedside treatment strategies will be critically
appraised (
Table 7.1
): (1) cell transplantation approaches to modulate in-
flammatory responses after SCI (stimulated macrophages), (2) replacement
of oligodendroglia in order to remyelinate axons in the injured spinal cord
(human embryonic stem cell, hESC-derived oligodendroglial precursor
cells). Further, approaches investigating molecular compounds like: (3) in-
hibition of the Rho pathway with BA-210 and (4) neutralization of Nogo-A
with specific antibodies, which aim to interfere with axon regrowth.
These four strategies will be reflected in the context of reported
preclinical evidence that triggered further development into clinical trials.
The detailed analysis of respective clinical trials will not be within the scope
of this review.
