Introduction
Moving
treatments from the preclinical to the clinical realms is
notoriously
difficult. For all diseases, only 10% of agents that enter phase 1
trials result in a clinically used drug.
1,2 The success rate in stroke and traumatic brain injury is also low and well-documented.
3–5
The translational failure in stroke has been attributed to the narrow
therapeutic window and to mistakes such as very broad inclusion
criteria, and imprecise, global outcome measures.
3–5 On the preclinical side, depth and rigor of study design, analysis and interpretation have received special focus.
Stroke recovery involves distinct biological principles and a very different time window compared to stroke neuroprotection.
6–8
Unlike acute stroke, post-stroke behavioral activity shapes recovery
and can be manipulated to promote recovery, or to negatively interact
with recovery.
6,9
In addition, stroke recovery involves a unique biology of altered
synaptic signaling, enhanced synaptic plasticity and changes in neuronal
circuits that provide novel drug and cellular targets but also raise
special considerations in clinical translation. The special
considerations include: the animal stroke models, the tissue and
behavioral outcome measures, imaging biomarkers and conceptual
management of the full translational pipeline.
Recent conceptual
and technological developments in neuroscience are bringing promising
physical, pharmacological and cellular therapies to the field of
neurorehabilitation and brain repair. This paper outlines a series of
guidelines and recommendations specifically tailored to enhance the
quality and rigor of preclinical stroke recovery research.
The task of the translational working group of the Stroke Recovery and Rehabilitation Roundtable (SRRR)
10
was to develop a set of guidelines and recommendations appropriate for
preclinical stroke recovery research. Existing preclinical stroke
research recommendation papers (e.g. STAIR, STEPS) focus chiefly on
acute stroke.
11,12 Although cognitive impairments and depression are common after stroke,
13
the SRRR working groups concluded that these topics require a
subsequent roundtable discussion so the emphasis here is on preclinical
sensorimotor recovery. The ultimate goal of the translational group was
to align preclinical to clinical stroke recovery studies so as to avoid
past mistakes and maximize clinical translation.
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