MC1R-Targeted Apoptotic Induction Followed by Melanocyte Stem Cell Transplantation: A Novel Therapeutic Strategy for Giant Congenital Melanocytic Nevus

Description: Giant Congenital Melanocytic Nevus (GCMN) is a rare congenital condition characterized by aberrant melanocyte proliferation affecting large areas of skin, including the face, with no current treatment achieving complete, safe resolution. This hypothesis proposes a three-stage targeted therapeutic strategy: Stage 1: A designed conjugate molecule (NDP-MSH + pH-sensitive linker + BH3 mimetic) selectively eliminates GCMN melanocytes via MC1R-mediated endocytosis and apoptotic induction — without affecting surrounding keratinocytes, nerve fibers, or vascular structures. Stage 2: Image-guided delivery using Line-field Confocal Optical Coherence Tomography (LC-OCT) ensures cellular-precision targeting at the dermal-epidermal junction. Stage 3: Autologous melanocyte stem cell transplantation repopulates the cleared niche with normally functioning melanocytes, restoring physiological pigmentation. This approach is supported by recent evidence confirming BCL2 overexpression in GCMN cells, and by established clinical outcomes in melanocyte transplantation for vitiligo