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Title: An exploratory study to investigate potential sensory biomarkers of chemotherapy-induced and diabetic peripheral neuropathy
Author: Narayanaswamy, Hema Malini
ISNI:       0000 0004 2715 9660
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Aims: Identification of neurophysiological or skin innervation biomarkers which can be used to assess and monitor progression of diabetic sensory polyneuropathy (DPN) and chemotherapy-induced neuropathy (CIPN). Sensitive and robust measures are needed to detect changes in the relatively short duration of clinical trials aimed to modify progression of neuropathy. Methods: 40 patients with DPN were studied longitudinally over 1 year, and 33 patients with CIPN in a cross-sectional study. Clinical assessments, questionnaires, quantitative sensory testing, histamine-induced skin flare, nerve conduction studies and contact heat evoked potentials were measured. Repeat skin biopsies were performed at a 6 month interval to quantify intra- (IENF) and sub-epidermal (SENF) nerve fibres immunoreactive for PGP 9.5 (pan-neuronal marker), TRPV1 (heat and capsaicin receptor) and GAP-43 (marker of regenerating fibres) in the DPN group, and at baseline in the CIPN group. Results: There was no change in symptoms and sensory tests in the DPN group. However, there was a significant reduction in IENF and SENF for both PGP 9.5 and TRPV1 fibres in the second DPN skin biopsy (n = 29 had repeat biopsy). GAP- 43 fibres were present in the dermis and remained unchanged. Patients in the CIPN group had less painful neuropathy, but similar abnormalities on examination and sensory tests. Despite this, a preserved number of IENF and SENF were seen in the CIPN group, with abnormal morphology. This has not been reported previously. Conclusion: PGP 9.5 and TRPV1-immunoreactive nerve fibres in sequential skin biopsies provide objective markers of progression of neuropathy, while the preserved GAP 43-immunoreactive fibres may detect enhanced regeneration. Novel findings in the CIPN group suggest prevention of degeneration and restoration of function should be the treatment strategy, rather than enhancing regeneration.
Supervisor: Anand, Praveen Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD)
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral