Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders

Studies of lysosomal storage diseases and channelopathy

S. Kano, M. Yuan, R. A. Cardarelli, G. Maegawa, N. Higurashi, M. Gaval-Cruz, A. M. Wilson, C. Tristan, M. A. Kondo, Y. Chen, M. Koga, C. Obie, K. Ishizuka, S. Seshadri, R. Srivastava, Takahiro Kato, Y. Horiuchi, T. W. Sedlak, Y. Lee, J. L. Rapoport & 6 others S. Hirose, H. Okano, D. Valle, P. O’Donnell, A. Sawa, M. Kai

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Methodologies for generating functional neuronal cells directly from human fibroblasts [induced neuronal (iN) cells] have been recently developed, but the research so far has only focused on technical refinements or recapitulation of known pathological phenotypes. A critical question is whether this novel technology will contribute to elucidation of novel disease mechanisms or evaluation of therapeutic strategies. Here we have addressed this question by studying Tay-Sachs disease, a representative lysosomal storage disease, and Dravet syndrome, a form of severe myoclonic epilepsy in infancy, using human iN cells with feature of immature postmitotic glutamatergic neuronal cells. In Tay-Sachs disease, we have successfully characterized canonical neuronal pathology, massive accumulation of GM2 ganglioside, and demonstrated the suitability of this novel cell culture for future drug screening. In Dravet syndrome, we have identified a novel functional phenotype that was not suggested by studies of classical mouse models and human autopsied brains. Taken together, the present study demonstrates that human iN cells are useful for translational neuroscience research to explore novel disease mechanisms and evaluate therapeutic compounds. In the future, research using human iN cells with well-characterized genomic landscape can be integrated into multidisciplinary patient-oriented research on neuropsychiatric disorders to address novel disease mechanisms and evaluate therapeutic strategies.

Original languageEnglish
Pages (from-to)138-145
Number of pages8
JournalCurrent Molecular Medicine
Volume15
Issue number2
DOIs
Publication statusPublished - Jan 1 2015

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Channelopathies
Lysosomal Storage Diseases
Fibroblasts
Myoclonic Epilepsy
Tay-Sachs Disease
G(M2) Ganglioside
Research
Phenotype
Preclinical Drug Evaluations
Translational Medical Research
Pathology
Neurosciences
Cell culture
Brain
Screening
Therapeutics
Cell Culture Techniques
Technology
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology

Cite this

Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders : Studies of lysosomal storage diseases and channelopathy. / Kano, S.; Yuan, M.; Cardarelli, R. A.; Maegawa, G.; Higurashi, N.; Gaval-Cruz, M.; Wilson, A. M.; Tristan, C.; Kondo, M. A.; Chen, Y.; Koga, M.; Obie, C.; Ishizuka, K.; Seshadri, S.; Srivastava, R.; Kato, Takahiro; Horiuchi, Y.; Sedlak, T. W.; Lee, Y.; Rapoport, J. L.; Hirose, S.; Okano, H.; Valle, D.; O’Donnell, P.; Sawa, A.; Kai, M.

In: Current Molecular Medicine, Vol. 15, No. 2, 01.01.2015, p. 138-145.

Research output: Contribution to journalArticle

Kano, S, Yuan, M, Cardarelli, RA, Maegawa, G, Higurashi, N, Gaval-Cruz, M, Wilson, AM, Tristan, C, Kondo, MA, Chen, Y, Koga, M, Obie, C, Ishizuka, K, Seshadri, S, Srivastava, R, Kato, T, Horiuchi, Y, Sedlak, TW, Lee, Y, Rapoport, JL, Hirose, S, Okano, H, Valle, D, O’Donnell, P, Sawa, A & Kai, M 2015, 'Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders: Studies of lysosomal storage diseases and channelopathy', Current Molecular Medicine, vol. 15, no. 2, pp. 138-145. https://doi.org/10.2174/1566524015666150303110300
Kano, S. ; Yuan, M. ; Cardarelli, R. A. ; Maegawa, G. ; Higurashi, N. ; Gaval-Cruz, M. ; Wilson, A. M. ; Tristan, C. ; Kondo, M. A. ; Chen, Y. ; Koga, M. ; Obie, C. ; Ishizuka, K. ; Seshadri, S. ; Srivastava, R. ; Kato, Takahiro ; Horiuchi, Y. ; Sedlak, T. W. ; Lee, Y. ; Rapoport, J. L. ; Hirose, S. ; Okano, H. ; Valle, D. ; O’Donnell, P. ; Sawa, A. ; Kai, M. / Clinical utility of neuronal cells directly converted from fibroblasts of patients for neuropsychiatric disorders : Studies of lysosomal storage diseases and channelopathy. In: Current Molecular Medicine. 2015 ; Vol. 15, No. 2. pp. 138-145.
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