Recovery of fine motor performance after ischemic damage to motor cortex is facilitated by cell therapy in the rhesus monkey

Abstract

We investigated the efficacy on recovery of function following controlled cortical ischemia in the monkey of the investigational cell drug product, CNTO 0007. This drug contains a cellular component, human umbilical tissue-derived cells, in a proprietary thaw and inject formulation. Results demonstrate significantly better recovery of motor function in the treatment group with no difference between groups in the volume or surface area of ischemic damage, suggesting that the cells stimulated plasticity.

Figure 1

Calibrated photograph of the lateral surface of motor and somatosensory cortices showing stimulation sites. Black circles represent sites that when stimulated produced a strong response of hand and/or digits and white circles represent sites that when stimulated produced weak or no response of hand and/or digits. Area of lesion within the sulcus is not shown in this photograph.

Figure 2

Representative thionin sections through the lesion from one control and one treated animal. Extent of lesion is visible to include surface representation of hand area and rostral bank of central sulcus.

Figure 3

Graph of difference scores on our Non-Human Primate Upper Extremity Motor Dysfunction Scale on measures of fine motor function and of hand strength from the first 3 days (d1–3) and last 3 days (d12–14 of initial post-operative period. Asterisks indicate a significant group difference in recovery of fine motor function (p<0.007) and the # indicates a significant difference in hand strength (p<0.02).

Figure 4

This graph shows the mean time to retrieve rewards across the entire 12-week post-operative testing period for the large well on the HDT. Asterisks indicate a significant group difference in the time required to retrieve rewards (p<0.001).

Figure 5

This graph illustrates a significant difference in performance between the control and treated groups in the initial week of testing with the treated animals having superior performance (*p<0.01). In addition, there was a significant difference in performance in the control group from the initial week to the final week of testing (#p<0.003). There was not a significant difference in the treated group during this time (p<0.217).

Figure 6

This graph illustrates the significant difference between groups for the number of post-operative days to attain asymptotic levels of grasp performance on the HDT for the impaired hand on the large well (p<0.01).

Figure 7

This graph demonstrates a significant difference between groups for the mean grasp assessment rating reached across the post-operative period on the HDT until criterion was reached on grasp assessment (p<0.01).