Development of a new CMT1A research toolbox: an alternative human stem cell-based strategy (R-12567)

With an overall prevalence of 1 in 2500 people, Charcot-Marie-Tooth disease (CMT) represents the most common hereditary peripheral neuropathy. Patients typically suffer from distally progressing muscle weakness, mild sensory loss to pain, foot deformities, or even loss of muscle stretch reflexes. To date, no effective treatments are available, highlighting the need for a better understanding of the underlying pathology. Different subtypes of the disease can be distinguished, with CMT1A being the most prevalent. CMT1A is an autosomal dominant demyelinating disease caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. This gene is mainly expressed by Schwann cells, where it plays an essential role in the development, maintenance, and stability of healthy myelin. Nevertheless, the exact mechanisms of how the PMP22 overexpression causes the CMT1A pathology is yet to be defined. Since the use of autologous primary human Schwann cells is restricted due to ethical issues, their low division rate, and overgrowth of fibroblast contamination in culture, little progress has been made in establishing new therapeutic approaches for CMT1A patients. Therefore, there is an urgent need for relevant and upscalable human cell culture models mimicking the CMT1A disease. We aim to develop a human dental pulp stem cell (hDPSC)-based in vitro model to study CMT1A-related disease mechanisms. hDPSC are isolated from the dental pulp of third molars and can be classified as a subtype of mesenchymal stem cells (MSC).

Keywords:CMT, Human stem cells, perifere myeline proteïne 22, Schwann cells, stem cell

Disciplines:Cell therapy