Striatal volume differences between non-human and human primates - PubMed (original) (raw)

Comparative Study

Striatal volume differences between non-human and human primates

Dali Yin et al. J Neurosci Methods. 2009.

Abstract

Convection-enhanced delivery (CED) has recently entered the clinic and represents a promising new delivery option for targeted gene therapy in Parkinson's disease (PD). The prime stereotactic target for the majority of recent gene therapy clinical trials has been the human putamen. The stereotactic delivery of therapeutic agents into putamen (or other subcortical structures) via CED remains problematic due to the difficulty in knowing what volume of therapeutic agent to deliver. Preclinical studies in non-human primates (NHP) offer a way to model treatment strategies prior to clinical trials. Understanding more accurately the volumetric differences in striatum, especially putamen, between NHP and humans is essential in predicting convective volume parameters in human clinical trials. In this study, magnetic resonance images (MRI) were obtained for volumetric measurements of striatum (putamen and caudate nucleus) and whole brain from 11 PD patients, 13 aged healthy human subjects, as well as 8 parkinsonian and 30 normal NHP. The human brain is 13-18 times larger than the monkey brain. However, this ratio is significantly smaller for striatum (5.7-6.5), caudate nucleus (4.6-6.6) and putamen (4.4-6.6). Size and species of the monkeys used for this comparative study are responsible for differences in ratios for each structure between monkeys and humans. This volumetric ratio may have important implications in the design of clinical therapies for PD and Huntington's disease and should be considered when local therapies such as gene transfer, local protein administration or cellular replacement are translated based on NHP research.

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Figures

Figure 1

Figure 1

Volume of right and left putamen, caudate nucleus and striatum in normal humans, in PD patients, in parkinsonian and normal Rhesus, and in normal Cynomolgus monkeys

Figure 2

Figure 2

MR images of putamen (green outline) in representative normal (A) and parkinsonian (B) Rhesus monkey

Figure 3

Figure 3. Comparison of representative MR images of putamen (outlined in green) from human PD patient (A) and normal Rhesus monkey (B)

The monkey striatum has been enlarged relative to the human to facilitate comparison.

Figure 4

Figure 4. Volume of putamen, caudate nucleus and striatum in normal human vs normal Rhesus monkeys, normal human vs Cynomolgus monkeys, and Parkinsonian patient vs Parkinsonian Rhesus monkey

H, human; R, Rhesus; C, Cynomolgus; PP, parkinsonian patient; PR, parkinsonian Rhesus. **, p < 0.0001. Ratiometric differences are indicated above each data set.

Figure 5

Figure 5. Comparison of representative MR images of from human (A) and Rhesus monkey (B) (putamen outlined in white)

The images are scaled to illustrate the 5-fold greater striatal volume of the human striatum compared to that of the Rhesus monkey.

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