Disease models

Patient-derived oligocortical spheroids could be used to study demyelinating diseases and screen therapies to treat them. The spheroids were generated by culturing human pluripotent stem cells with platelet derived growth factor AA (PDGFAA), insulin-like growth factor-1 (IGF-1) and thyroid hormones to produce spheroids containing neurons, astrocytes and oligodendrocytes. In the oligocortical spheroids, the generics clemastine and ketoconazole, which promote myelination, increased the number of oligodendrocytes compared with vehicle. Oligocortical spheroids generated from patients with Pelizaeus-Merzbacher disease, a demyelination disease caused by proteolipid protein 1 (PLP1) mutations, had lower numbers of oligodendrocytes than oligocortical spheroids derived from healthy controls, and in the patient-derived spheroids, CRISPR-based editing of the PLP1 mutation or a tool compound that mobilizes PLP1 from the endoplasmic reticulum to oligodendrocyte processes increased the number of oligodendrocytes compared with no treatment. Next steps could include using the oligocortical spheroids to generate models other demyelinating disorders and screen for remyelinating compounds.

Clemastine is marketed to treat allergies...