Gene therapy for global brain diseases: one small step for mice, one giant leap for humans

Abstract

This scientific commentary refers to ‘Global CNS correction in a large brain model of human alpha-mannosidosis by intravascular gene therapy’, by Yoon et al. (doi:10.1093/brain/awaa161).

Figure 1

Neuronal architecture in lissencephalic and gyrencephalic mammals. (A) Neuronal types in layer VI of the cerebral cortex of the mouse (Mus musculus). ax = axons; FP = flattened pyramidal neuron; H = horizontal neuron; HP = horizontal pyramidal cell; IP = inverted pyramidal neuron; LP = large pyramidal neuron; M = Martinotti cell; S = multipolar neuron with locally arborizing axon; SP = small pyramidal neuron. *Multi-apical pyramidal cells. Scale bar = 100 µm. (B) Camera lucida drawing of neurons in the sixth layer of the (i) gyral and (ii) fissural regions of the cat cerebral cortex. aP = atypical pyramidal cells; B = bipolar cells; F = fusiform neurons; LC = local circuit neuron; P = pyramidal neuron. *Inverted pyramidal cell in the gyrus and a horizontal pyramidal cell in the fissural region. Small arrows point out the course of the axons and collaterals. (C) Neurons in the sixth layer of the (i) gyrus and (ii) sulcus of the cerebral cortex of the human infant. B = bipolar neuron; LC = local circuit neuron; sMp = spinous multipolar neuron with long descending axon. *Inverted pyramidal cell in C(i), and a tangential (horizontal) pyramidal cell in C(ii). Reproduced with permission from Ferrer et al. (1986a, b).