Biology Reference
In-Depth Information
apparent benefit and our dose-response curve was bell shaped for the cervical
patient population (
Fehlings et al., 2011
). Across all dose groups, the change in
motor score was 18.6
19.3. Patients in the 3 mg dose group showed a
27.3
13.3-point improvement, over double the expected recovery.
Recent analysis of the natural history of motor and sensory recovery after
SCI from the Sygen and EMSCI data (
Fawcett et al., 2007; Steeves et al.,
2011; Zariffa et al., 2011
) has been informative as historical comparison
with the Cethrin trial results. Patients are expected to improve
approximately 10 motor points on the ASIA scale. Our observed
27-point improvement in the 3 mg dose would provide patients with
greater than two-segment recovery of motor levels, which is functionally
very significant for the patients, allowing a change from being fully
dependent to being independent in self-care. While early surgery can be
beneficial to patients (
Fehlings et al., 2012
), most of the patients in the
Cethrin trial were recruited later than 24 h. The comparison of patient
improvement with time of Cethrin treatment shows that the increase in
motor score is not explained by the timing of
treatment, providing
further suggestion of the efficacy of the drug.
4. SUMMARY
There are approximately 12,000 new spinal cord injuries each year in
the United States, and about half of these injuries are cervical injuries. The
relatively small patient population masks the huge burden these patients
place on the health care system. At present, there are no clinical treatments
available to stimulate regeneration of cut axons, but with the pace of research
in the field of CNS axon regeneration now increasing, the availability of
new drugs to treat patients may not be far away. The Cethrin clinical trial
has showed safety in patients, and further clinical studies are planned to
determine in double-blind studies if Cethrin is effective to promote mean-
ingful functional recovery for patients. Numerous studies show that anatom-
ical regeneration and functional recovery are possible in rodent models of
SCI. New drug development is badly needed in the field of neurotrauma.
Clinical treatments that foster regeneration and are safe enough for long-
term treatment need to be developed. New treatments might be synergistic
with present treatments that are in clinical development for the critical care
period. Since Rho is a well-validated pathway, new drug development for
additional targets in the Rho signaling pathway will be a promising avenue
to translate toward clinical development.
