Aim 1: Demonstrate mitochondrial respiration efficiency of PBMCs inversely correlates with clinical symptoms of NF1 patients. We will use Seahorse XF Pro analysis to measure cellular and mitochondrial bioenergetics of PBMC isolated from NF1 patients. We predict patients with milder symptoms of fatigue, pain, liver and cardiac function, creatine kinase (CK) and body mass index (BMI) will demonstrate better mitochondrial function in their circulating cells.
Aim 2: Assess whether therapeutic interventions impact mitochondrial function and metabolic plasticity of circulating cells of NF1 patients. We hypothesize that MD among NF1 patients sensitize them to therapeutic interventions targeting mitochondria. We will assess the impact of vitamin D treatment to potentially improves mitochondrial function and explore if MEK inhibitors like Koselugo (KOS, Selumetinib, FDA-approved treatment of plexiform neurofibromas in NF1) harm mitochondrial function in patients with NF1, due to their impact in RAS pathway (24). We predict the impact of treatments on mitochondrial function will lead to insights on mechanisms of action for NF1 patients and possibly serve as diagnostic and/or prognostic biomarkers for patient outcomes.

MRE grant

2022-09-16

2023-09-16