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Current PNRR Publications

Peripheral Neuropathy Research Registry (PNRR) Published Papers

Plasma proteomic analysis on neuropathic pain in idiopathic peripheral neuropathy patients

November 21, 2023
Why only half of the idiopathic peripheral polyneuropathy (IPN) patients develop neuropathic pain is unknown. By conducting a proteomics analysis on IPN patients, proteins and new pathways that are associated with neuropathic pain were discovered.

The lipidomic component of the biomarker study identified a unique signature of changes in lipid levels in idiopathic peripheral neuropathy patients with pain versus no pain.  This opens up the possibility of developing a new blood test to objectively measure pain level in patients with PN. This potentially could alter how we assess patients with neuropathic pain and how we treat them. The findings also point to new mechanisms of pain. JHU is working on exploring the feasibility of taking these observations from patient samples to mouse models of PN.

Authors: Perry T.C. van Doormaal, MD, PhD; Simone Thomas, MS; Senda Ajroud-Driss, MD; Robert N. Cole; Lauren R DeVine; Mazen M Dimachkie, MD; Stefanie Geisler, MD; Roy Freeman, MD; David M. Simpson, MD; J Robinson Singelton, MD; A. Gordon Smith, MD, FAAN; Amro Stino, MD; Ahmet Höke, MD, PhD; PNRR Study Group

Citation Information:

Exploratory Analysis of Peripheral Neuropathy Patient Biomarker and Symptom Characteristics (Master Thesis)

October 20, 2023
This study utilized Machine Learning algorithms on PNRR data variables to run exploratory data analyses and assess and describe clusters for PN with regard to patient, symptom, nerve conduction, and bloodwork characteristics. Machine Learning algorithms used in this manner identified clusters of different causes of PN and how these causes are correlated with PN disease manifestation. Ultimately, with these findings, the hope is to aid in predicting and identifying better diagnostic causes of diabetic and idiopathic PN.

Author: Julien Biland (Zurich University of Applied Sciences)

Link to thesis:

Vitamin B6 levels do not correlate with severity of neuropathy in chronic idiopathic axonal polyneuropathy

December 21, 2021
In this study, researchers asked if elevated plasma vitamin B6 levels were related to outcomes measures in a well-characterized cohort of patients with chronic idiopathic axonal polyneuropathy (CIAP). It was concluded that vitamin B6 levels do not correlate with the severity of neuropathy. Please click here for full publication.

Authors: Simone Thomas, MS; Sarah Stewart, BA; Erol Höke; David M. Simpson, MD; J. Robinson Singleton, MD; Ahmet Höke, PhD, MD

Citation information: J Peripher Nerv Syst. 2021:


A circulating, disease-specific, mechanism-linked biomarker for ATTR polyneuropathy diagnosis and response to therapy prediction​​

December 17, 2020
In collaboration with the Kelly Laboratory, Protego Biopharma has developed an ELISA specific for non-native transthyretin that is being proposed to use as a diagnostic/prognostic assay in patients with Familial Amyloidotic Polyneuropathy (FAP) related to transthyretin deposition and carriers of mutations responsible for the disease. This study probed the biochemical mechanisms of amyloid diseases using 40 PNRR plasma samples (as a control), from idiopathic, chemotherapy-induced and diabetic peripheral neuropathy patients between the ages of 30 and 70, half male, half female. The researchers have currently concluded that their assay was able to detect biochemical markers of FAP in both pre-symptomatic and diagnosed FAP patients. The non-FAP controls from the PNRR patient samples did not show those biochemical markers, suggesting that this assay can be useful in diagnosing FAP. A second publication is expected to come out from this study. Please click here for current publication.

CONTRIBUTORS: Xin Jiang; Richard Labaudinière; Joel N. Buxbaum; Cecília Monteiro; Marta Novais; Teresa Coelho; Jeffery W. Kelly

Citation information: PNAS 2021:

Relation of exercise and pain in patients with idiopathic distal axonal polyneuropathies​

October 6, 2020
This study was completed to do a comprehensive data analysis about the benefits of regular exercise in a well‐characterized cohort of patients with idiopathic distal, symmetrical, axonal polyneuropathy enrolled in the Peripheral Neuropathy Research Registry (PNRR) at Johns Hopkins University School of Medicine. The data suggests that patients with idiopathic neuropathy benefit from exercises even if performed on a low intensity level or less frequently, and patients are less likely to have severe pain symptoms when exercising on a regular basis. Please click here for full publication.

Authors: Simone Thomas, MS; Sarah Stewart, BA; Perry T.C. van Doormaal, PhD, MD; Ahmet Höke, PhD, MD

Citation information: J Peripher Nerv Syst. 2020;

Peripheral Neuropathy Research Registry: A Prospective Cohort

January 4, 2019
Descriptive paper of the PNRR cohort as a multi-center collaboration initiated and funded by the Foundation for Peripheral Neuropathy (FPN) with the objective to build a well-characterized cohort of patients with different peripheral neuropathy phenotypes. Information from the first 1150 patients enrolled in the study was analyzed to document observed differences between idiopathic, diabetic, HIV- and CIPN-induced PN. Statistical analysis was not included in the paper. Please click here for full publication.

Authors: Simone Thomas, MS; Senda Ajroud-Driss, MD; Mazen Dimachkie, MD; Christopher Gibbons; Roy Freeman, MD; David M. Simpson, MD; J. Robinson Singleton, MD; A. Gordon Smith, MD, FAAN; PNRR Study Group; Ahmet Höke, PhD, MD

Citation Information: J Peripher Nerv Syst. 2019;24:39–47.,

NaV Channel Variants in Patients with Painful and Non-Painful Peripheral Neuropathy​

July 25, 2017
Next-generation sequencing was performed on DNA samples of 278 idiopathic (67% painful and 33% nonpainful) and 179 diabetic distal polyneuropathy patients (77% painful and 23% nonpainful) to examine the incidence of nonsynonymous missense variants in SCN9A (NaV1.7), SCN10A (NaV1.8), and SCN11A (NaV1.9). There were no significant differences in missense variant allele frequencies of any gene, or SCN9A haplotype frequencies, between PNRR patients with painful or non-painful peripheral neuropathy. PNRR patient SCN9A and SCN11A missense variant allele frequencies were not significantly different from the Exome Variant Server, European American (EVS-EA) reference population. For SCN10A, there was a significant increase in the alternate allele frequency of the common variant p.V1073A and low-frequency variant pS509P in PNRR patients compared with EVS-EA and the 1000 Genomes European reference populations.

Authors: Samir Wadhawan, PhD; Saumya Pant, PhD; Ryan Golhar, PhD; Stefan Kirov, PhD; John Thompson, PhD; Leslie Jacobsen, MD; Irfan Qureshi, MD; Senda Ajroud-Driss, MD; Roy Freeman, MD; David M. Simpson, MD; A. Gordon Smith, MD, FAAN; Ahmet Höke, PhD, MD; Linda J. Bristow, PhD

Citation Information: