Een patiënt-in-een-schaal model voor Charcot-Marie-Tooth type 1A: een nieuwe aanpak om de rol van perifeer myeline proteïne 22 te onderzoeken in de pathogenese van deze ziekte (R-10006)

Charcot-Marie-Tooth (CMT) disease is the most common inherited neurological disorder, affecting about 1 in 2,500 people worldwide. The most common form of the disease, CMT type 1A is caused by a duplication of the Peripheral Myelin Protein 22 (PMP22) gene located on chromosome 17. PMP22 is a critical component of the myelin sheath formed by Schwann cells and overexpression of this gene causes the structure and function of the myelin sheath to be abnormal. Patients with CMT1A therefore experience severe weakness and atrophy of the muscles of the lower legs beginning in adolescence; later they experience hand weakness and sensory loss. At present it is unclear what the role is of PMP22 in the pathogenesis of the disease and data in patients are missing. In this research project, we therefore develop a "patient-in-a-dish" model by differentiating CMT1A patient-derived induced pluripotent stem cells (iPSC) and dental pulp stem cells (DPSC) toward Schwann cells. These cells are used in several in vitro assays and in an in vivo mouse model for peripheral nerve injury, in order to explore the role of PMP22 in the disease and how it affects myelination. Moreover, we try to restore the genetic defect with the novel and promising CRISPR interference technology. The outcome of this study is of high clinical importance and can be a prototype for the treatment of other diseases of the peripheral or central nervous system in which myelin deficits are involved.

Trefwoorden:STAMCELLEN

Disciplines:Celtherapie, Neurologische en neuromusculaire ziekten