Assessing Pain Linked to High Metabolic and Glycolytic Shift in Neurofibromatosis Type 1 (NF1) Patients by Using a Bioenergetic Biomarker: A Pilot Study

Background and objective Neurofibromatosis type 1 (NF1) is a common, incurable genetic disorder that causes neuronal tumors and other symptoms. Emerging evidence suggests that neurofibromin mutations dysregulate mitochondrial metabolism. We developed and tested a biomarker approach for the first time to assess mitochondrial dysfunction among NF1 patients and its association with adverse health outcomes. Methods We conducted a prospective observational clinical study, enrolling 44 NF1 patients and 11 controls without neurofibromin defects. We isolated peripheral blood mononuclear cells (PBMCs) from the subjects and measured mitochondrial function. Patient data were collected from biomedical evaluations and questionnaires assessing fatigue and pain; these results were then correlated with mitochondrial measurements. Results NF1 led to significant differences in the extracellular acidification rate (ECAR) (p = 0.008) but not in oxygen consumption rates (OCR). The OCR versus ECAR plot indicated a glycolytic bias in NF1 patients. Patient-reported pain was positively correlated with OCR (p = 0.003) but not with ECAR (p = 0.4). There were no correlations observed for fatigue. The severity of pain and fatigue were also positively correlated (p < 0.002). Conclusions This pilot project was the first study in humans to suggest that NF1 patients may have a dysregulation in cellular respiration towards less aerobic, more glycolytic metabolism. Additionally, the findings suggest that the pain experienced by NF1 patients may be linked to this energy dysfunction.