Cellular Models Derived from Patients for Polytarget Precision Medicine in Neurodegeneration Associated with Pantothenate Kinase

Abstract

A wide range of progressive and incapacitating neurological hereditary illnesses in which iron is selectively accumulated in
certain brain regions are together referred to as neurodegeneration with brain iron accumulation (NBIA).Pantothenate kinase-associated neurodegeneration (PKAN), the most common subtype of NBIA diseases, is brought on by pathologic variations in the PANK2 gene, which codes for the enzyme pantothenate kinase 2 (PANK2). There are currently no proven ways to halt the growth of these illnesses. The usefulness of patient-derived cell models as a useful instrument for identifying natural or pharmacological substances for the use of polytarget precision medicine in PKAN is covered in this study. According to a number of recent research, fibroblasts produced from PKAN patients exhibit the primary pathogenic characteristics of the illness, such as intracellular iron excess.
Interestingly, all pathologic changes in PKAN fibroblasts with residual expression of the PANK2 enzyme were improved when mutant
cell cultures were treated with different supplements as pantothenate, pantethine, vitamin E, omega 3, α-lipoic acid, L-carnitine, or
thiamine. the data from pharmacological screens in patient-derived cellular models may be used to improve treatment plans for specific PKAN patients.