Current Research


A. Research Projects for which serum, plasma and/or DNA was provided together with data:

Biomarker Study / Johns Hopkins University (2016 – ongoing):


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 is currently being confirmed in a validation cohort (2019). If confirmed, 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.

The other components of the biomarker study were the examination of metabolites and proteins. No significant findings were observed in those evaluations.

Plumeria / Rutgers University (October 2018 – ongoing):

Study on inflammation and neuropathic pain, specifically on Caucasian patients with diabetic neuropathy. 164 subjects (DNA, serum and plasma) were acquired from both painful DPN and non-painful DPN, both female and male.

Study performed a genetic analysis on diabetic neuropathy patients with painful symptoms and non-painful symptoms. Gender was also closely monitored in this study. The analyses were set up to identify potential correlation between chemokine system genetic variations and that of neuropathic pain and to determine the CCR2 receptor genetic variations and isoform mRNA profiles.

This research aimed to diagnose patients with genetic susceptibility to pain, thus help in treatment options as well as to provide molecular information about the chemokine system in general (and the CCR2 receptor in particular) so that drug development efforts may be better targeted to the specifics of the CCR2 receptor.

Disarm Therapeutics (May 2019 – ongoing):

Study to identify a sensitive biomarker (Neurofilament light (NF-L)) of axonal degeneration, by which diabetic neuropathy onset can be identified at an earlier stage. Identification may be a means to target patients who are at risk for development of severe DPN. The purpose of this study is to measure NF-L levels in 30 diabetic patients with and without evidence of, as it may be a useful market for determining the effectiveness of a drug intended to prevent and/or decrease DPN. 30 DPN Serum samples were provided – 10 with normal sural nerve amplitude, 10 with at least one side with no response, and 10 with reduced sural nerve amplitude.

Cambridge University (2019 – ongoing):

Injured axons undergo a preventable degeneration mechanism known as Wallerian degeneration. Work in animal and cell culture models suggests CIPN involves activation of this same mechanism.

This study aims to involve this pathway in 101 CIPN (blood) samples by genetic association methods in order to establish Wallerian-blocking drugs that are currently being developed, and to discover methods to predict who is at risk. This is also important in view of recent animal data indicating a role for the Wallerian degeneration pathway in diabetic neuropathy.

Johns Hopkins / Washington University (2019 – ongoing):

Whole genome testing is proposed for patients with idiopathic neuropathy currently enrolled in PNRR to identify new genes or genetic risk factors for polyneuropathy. At the moment, limited funding is available for the project allowing to analyze a maximum of 300 samples. The PNRR data set was screened for candidates with a high yield for potential genetic markers based on their personal and family medical history information and 275 candidates were identified.

This research led by Dr. Ahmet Höke (Johns Hopkins University School of Medicine) and Dr. Jeffrey Milbrandt (Washington University at St. Louis) will not just analyze for unknown variants in the genes known to cause PN, but will also evaluate for those genes that are involved in regulating the presence of a specific protein. Whole Genome Sequencing (WGS) has been very costly in the past, but advanced technology developed over the past few years has reduced the cost significantly, making this research possible. As additional funding becomes available, WGS will be performed with more samples. 275 samples will not be enough for statistical analysis, but it might be enough to find some genome sequences that show variation in high percentages of tested patients.

In October 2020, an additional 398 samples were distributed to Washington University to further the research.

The Scripps Research Institute (2021 – ongoing):

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 related to transthyretin deposition and carriers of mutations responsible for the disease.

This study will probe the biochemical mechanisms of amyloid diseases with 40 plasma samples, studying idiopathic, chemotherapy-induced and diabetic peripheral neuropathy patients between the ages of 30 and 70, half male, half female.

The study, which is anticipated to be completed in six months, will also use the assay to determine target engagement by various therapeutics either in use or in development for the treatment of these disorders.

Please click here to read “A circulating, disease-specific, mechanism-linked
biomarker for ATTR polyneuropathy diagnosis
and response to therapy prediction,” a publication associated with this project.

Northwestern University (2022 – ongoing):

Metabolomics, an emerging and rapidly evolving
field, has been highlighted as one of the broadest
and more reliable tools for physiological status
investigation, discovery of new biomarkers, and
metabolic pathway analysis. Metabolomics involves quantitative detection of a large number of small molecule metabolites in biological system, and their steady-state levels can be regarded as the
ultimate response of biological systems to
genotype, phenotype, and environment.

This study will utilize metabolomics to identify novel plasma metabolomic signatures associated with diabetic neuropathy.

UCL Institute of Neurology (2022 - ongoing):

This project will provide insight into possible genetic modifiers of oxaliplatin-induced CIPN (chemo-induced peripheral neuropathy), which could lead to better patient stratification and identification of a possible drug target.

UCL Institute of Neurology (2022 - ongoing):

Preventable Axon Degeneration in Human Disease. Wallerian degeneration (WD) is a well-characterized axon degeneration program. The aim of this study is to test whether CIPN and DPN is influenced by WD by screening for contributory mutations from these cohorts using exome sequencing.

Johns Hopkins University (2023 - ongoing):

Neurofilament Light Chain Plasma Levels in a Large Cohort of Patients with Cryptogenic Sensory Polyneuropathy (CSPN). Neurofilament light chains (NfL) are associated with axonal degeneration, and elevated NfL levels have been observed in many neuromuscular diseases such as amyotrophic lateral sclerosis ALS, multiple sclerosis (MS), or Parkinson’s disease. More recently, elevated NfL levels were also confi rmed in sensory polyneuropathies such as diabetic, chemotherapy-induced, and amyloid polyneuropathies. This suggests NfL plasma level as a potential biomarker to monitor disease activity in polyneuropathies, which would be of particular interest for future intervention trials. This project will measure NfL levels using SIMOA assay.

B. Data Analysis Projects:

Washington University (2019 – ongoing):

An analysis of CIPN data set (120 enrollments) induced by different chemotherapeutic drugs by characterizing the phenotypes of acquired neuropathies.

Of the 120 patient samples used that were diagnosed with CIPN, 36 were treated with platin derivatives, 24 with taxanes, 15 with vinca alkaloids (vincristine), 15 with proteasome inhibitors (bortezomib), 13 with a platin drug plus taxane (platin/taxane) and 17 with other chemotherapeutics.

As CIPN symptoms vary depending on drug class, a careful characterization of CIPN phenotypes induced by different chemotherapeutic drugs have indicated that patient reported symptoms and exam findings are not always consistent, suggesting that patients require a careful neurological and electrodiagnostic evaluation to assess the full extent of CIPN.

Johns Hopkins University (2019 – ongoing):

Student Project: Comparison of symptoms and severities of PN in patients who are pre-diabetic versus those with metabolic syndrome (with and without prediabetes); patients enrolled as idiopathic who have neither prediabetes nor metabolic syndrome function as the control group. The data analysis includes the data records of 400 patients enrolled in PNRR.

ZHAW Zurich University of Applied Sciences (February – September 2022):

Student Project: This study will utilize 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 can potentially identify 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 idiopathic PN.

University of Kansas (2022 – ongoing):

Student Project: Distal sensory loss and reduced or absent ankle jerk tendon reflex are the most common onset symptoms for polyneuropathy. Some studies indicate that age as well as height influence the presence of the ankle reflex, and both height and age are some of the well-established factors that influence abnormal outcomes of Nerve Conduction Studies (NCS). This study will utilize the PNRR data of all patients enrolled with diagnosis of idiopathic polyneuropathy, to evaluate for the effects of patient height and age and its influence on sural nerve sensory action potential parameters and ankle tendon reflex responses.

University of Kansas (2022 – ongoing):

Student Project: Myopathy (muscle weakness) is more common in patients with diabetic PN compared to those with idiopathic PN. Analyses will be performed on data records of 120 diabetic PN patients enrolled in the PNRR, checking for frequency and severity of myopathy in patients with DPN compared to those with idiopathic PN, as well as other variables (such as glycemic control, age, pain severity, medications or duration of diabetes diagnosis) contributing to the presence of myopathy.

University of Kansas (2022 – ongoing):

Student Project: Data from 120 patients with diabetic PN (DPN) will be compared to the data of 120 patients with idiopathic PN (IPN) to evaluate for the frequency, pattern (motor versus sensory) and degree of demyelinating properties measured by Nerve Conduction Studies (NCS) in patients with DPN compared to those with IPN.

University of Cincinnati (2022 – ongoing):

Retrospective case-control study. Goal is to identify the clinical characteristics of neuropathies associated with metabolic syndrome (MetSyn). Hypothesis is that patients with MetSyn neuropathy have a different phenotype in comparison to patients who do not fulfill MetSyn criteria, and that each MetSyn component has different degrees of contribution to neuropathy. Data collected from 487 PN patients (144 diabetic PN; 343 idiopathic PN) will be analyzed.

University Hospital Basel (2023 – ongoing):

Characterization of patients with idiopathic small-fiber neuropathy: An epidemiologic study based on the Peripheral Neuropathy Research Registry (PNRR). Preliminary evidence suggests dysimmune/inflammatory causes to play a major role in the pathomechanism of some patients with idiopathic SFN, and that these may be over-represented among patients with nonlength dependent SFN (NLSFN), but RCTs with IVIG (an anti-inflammatory) have not yielded significant results, which suggest that idiopathic SFN is caused by several different mechanisms. The proposed project aims to evaluate whether specific key variables are differentially distributed between pre-defined subgroups of patients with ‘idiopathic’ SFN in comparison to patients with SFN due to diabetes, chemotherapy, or HIV in the PNRR