Human Tridimensional Neuronal Cultures for Phenotypic Drug Screening in Inherited Peripheral Neuropathies

Renata Maciel, Renata Correa, Juliana Bosso Taniguchi, Igor Prufer Araujo, Mario A. Saporta

Research output: Contribution to journalArticle


Length-dependent axonal degeneration is the pathologic hallmark of several neurodegenerative disorders, including inherited peripheral neuropathies (Charcot-Marie-Tooth (CMT) disease). CMT is currently an untreatable disorder. This is partially due to lack of translational models suitable for drug discovery. In vitro models of CMT have been hindered by the 2D configuration of neuronal cultures, which limits visualization and orientation of axons. To overcome these limitations, we cultured induced pluripotent stem cell (iPSC)-derived spinal motor neurons as 3D spheroids, which grow axons in a centrifugal fashion when plated. Using these iPSC-derived spinal spheroids, we demonstrate neurofilament deposits in motor neuron axons of three patients with CMT2E, caused by mutations in the NEFL gene. This phenotype is partially reversed by two kinase inhibitors. In summary, we developed a human tridimensional in vitro system that models length-dependent axonopathies, recapitulates key pathophysiologic features of CMT2E, and should facilitate the identification of new therapeutic compounds for CMT.

Original languageEnglish (US)
Pages (from-to)1231-1239
Number of pages9
JournalClinical Pharmacology and Therapeutics
Issue number5
StatePublished - May 1 2020


ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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