have shown that in myelinoids, human myelination can be pharmacologically manipulated in a quantifiable manner at both cellular and global levels across the myelinoids. Therefore, myelin organoids can be used as a preclinical model for evaluating myelin associated candidate therapeutics and drugs in a human physiologically relevant context. Promyelinating drugs Myelin organoids can be used to study the therapeutic potential of possible myelination strategies for individuals with diseases associated with demyelination such as leukodystrophies and multiple sclerosis, an auto-immune demyelinating disease affecting the CNS. Clemastine and ketoconazole are promyelinating drugs that function as potent stimulators of oligodendrocyte generation and myelination in rodent models. The previously known effects of both drugs have been recapitulated using myelin organoids as they enhanced and accelerated the extent and rate of oligodendrocyte generation, maturation and myelination in organoids. ER Stress Pathway Small-Molecule Modulators Certain classes of pelizaeus-Merzbacher disease (PMD), Proteolipid protein 1 (PLP1) show perinuclear retention in oligodendrocytes. Perinuclear retention of misfolded proteins is a hallmark of endoplasmic reticulum (ER) stress, which might be implicated in the pathology observed in PMD. In a myelinoid model of Pelizaeus-Merzbacher disease (PMD) developed by Madhavan et al., treatment with a modulator of ER stress pathways called GSK2656157, an inhibitor of protein-kinase-R-like ER kinase, partially rescued PLP1 perinuclear retention mobilizing it away from the ER and into the processes of oligodendrocytes. In addition, treatment resulted in an increase in the number of cells that show MYRF expression, an oligodendrocyte specific transcription factor, which has been observed to be reduced in PMD oligodendrocytes compared to control. Gene-Editing: CRISPR In a myelinoid model of PMD caused by point mutations in Proteolipid protein 1 (PLP1), a CRISPR correction to the wildtype sequence in the hPSCs used to generate it rescued some aspects of PMD pathology. The treatment restored the perinuclear retention of PLP1 and mobilization into oligodendrocyte processes and increased the amount of oligodendrocytes that express MYRF, an oligodendrocyte specific marker, to levels observed in healthy controls. The myelin organoids derived from hPSC after the CRISPR correction of PLP1 point mutations generated myelin after 20 weeks in culture. Disease study Myelinoids recapitulate various fundamental aspects of brain development and myelination, and therefore related disease and pathology. Given that, they can be used to model various diseases and understand disease mechanisms associated with myelin defects including neurodegenerative diseases, CNS injury, PMD, and NFASC. Pelizaeus-Merzbacher disease (PMD) PMD is a rare monogenic disease caused