Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of disorders that commonly affect the long fibers of the corticospinal tract and posterior columns in the spinal cord, leading to progressive gait disturbances with muscle weakness and spasticity. Mutations in SPAST account for the largest group of adult-onset HSP cases and about 40-44% of all autosomal dominant ‘uncomplicated’ HSP. Using the patient-derived stem cell models established by our group we demonstrated that the acetylated alpha tubulin level is down-regulated in SPAST mutant and the velocity of peroxisome trafficking is slower comparing to the healthy controls. Tubulin interfering drugs taxol, vinblastine and EpoD at very low concentrations can rescue tubulin expression and recover the impaired peroxisome trafficking without changing cell proliferation, as indicated by MTS assay and EdU labeling. These drugs were not cytotoxic after culturing the cells for 24 hours and 7 days in these low doses, suggesting the therapeutic potential. The mechanism of peroxisome-trafficking rescue is still not clear but the Western blotting investigation suggests that these tubulin interfering drugs do not affect the tubulin-severing protein SPAST and stathmin, which have been demonstrated changed in the SPAST patient-derived stem cell model.