Current Research
A. Research Projects for which serum, plasma and/or DNA was provided together with data:
Sangamo Therapeutics (2023 – ongoing):
Anti-AAV antibody assay development to support clinical development of an investigational drug to treat chronic neuropathic pain. The validated assay will be used to support patient enrollment in the clinical trials. Samples will be used to support anti-AAV antibody assay development. 33 donor samples will be used for anti-AAV antibodies analytical validation to support assay cutoff determination and to demonstrate consistency in the test results.
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):
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.
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.
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 of Kansas (2023 – ongoing):
Nerve Entrapments in Patients with Peripheral Polyneuropathy. Student project. The correlation between diabetic PN and nerve entrapment in form of CTS (carpal tunnel syndrome) and UNE (ulnar nerve entrapment) is well documented. However, it has never been investigated in a large cohort of patients with idiopathic PN. This data analysis project will investigate the occurrences of CTS and UNE within the PNRR cohort of patients with a primary diagnosis of idiopathic polyneuropathy.
University of Michigan (2023)
Metabolic Syndrome and PN: Statistician Project (FPN funded). This study primarily aims to investigate the association between Metabolic Syndrome and its constituent components to, the severity of neuropathy, fiber type involvement, and neuropathy symptoms with specific focus on neuropathic pain. COMPLETED
Johns Hopkins (2024 – ongoing):
Student project. Comparison of the Utah Early Neuropathy Score (UENS) with the Total Neuropathy Score reduced (TNSr) in a cohort of patients with idiopathic, distal, symmetrical, axonal polyneuropathies. In the past 40 years, multiple attempts have been made to develop accurate scoring scales to assess the severity of peripheral neuropathies (PN) in a clinical setting. The majority of these severity scores were developed diabetic peripheral neuropathy (DPN) as this is the most common underlying etiology, counting for about half of all PN’s.
Two of the scores previously validated for DPN and chemotherapy-induced peripheral neuropathy (CIPN) were considered good matches for the idiopathic patient cohort enrolled in the Peripheral Neuropathy Research Registry (PNRR): the Utah Early Neuropathy Score (UENS) (Singleton, 2008) and the Total Neuropathy Score reduced (TNSr) (Smith, 2011).
Both scores were calculated for about 400 idiopathic PNRR participants for this evaluation to assess if either of these two scores are good matches for a cohort of patients with idiopathic peripheral neuropathy.
University of Rochester (2024 – ongoing):
Exploring symptom pattern presentation between distal sensory polyneuropathies conditions. Painful diabetic peripheral neuropathy (DPN) has been crucial in developing analgesic drugs like pregabalin and duloxetine, which are also used off-label for various peripheral neuropathic pain conditions. Recently, drug companies have shown interest in clinical trials for other distal sensory polyneuropathies (DSPs) such as chemotherapy-induced peripheral neuropathy (CIPN) and idiopathic small fiber neuropathy (iSFN). Recruiting for these trials is challenging, often requiring over 100 sites due to restrictive entry criteria. To improve recruitment and efficiency, broadening the target population to include DSPs of any cause is suggested, as they share a common “stocking glove” distribution of symptoms. It is argued that symptom variability within a single DSP condition is comparable to that between different DSP conditions. Using data from the Peripheral Neuropathy Research Registry (PNRR), this hypothesis will be tested, which, if confirmed, would support the feasibility of combining various DSP conditions in clinical trials to enhance recruitment and accelerate the development of new analgesics.
Vertex Pharmaceuticals (2024 – ongoing):
Feasibility Assessment of a Natural History Study on Painful Peripheral Neuropathy. The proposed study is a feasibility assessment to gain a better understanding of the data collected for the peripheral neuropathy patients in the PNRR, separately for diabetic peripheral neuropathy, chemotherapy-induced PN, idiopathic PN, and HIV/AIDS PN. The researchers would like to understand the sample size, clinical characteristics, and pain characteristics, in addition to the availability of longitudinal data, to determine if a longitudinal natural history study of painful peripheral neuropathy is feasible. Availability of longitudinal pain scores will be essential to understand real-world changes in pain experiences, especially when considering the use of different pain medications. Subsequently, findings from a potential future natural history study would increase our understanding of what individuals with painful DPN, and other peripheral neuropathies, are experiencing over time.
Johns Hopkins (2025 – ongoing):
Exploring Subgroups of Idiopathic Neuropathy Using Unsupervised Machine Learning: A complementary study to whole genome analysis. Although idiopathic PN is considered a single entity, there are likely differences among patients in terms of etiology and clinical features. This study will utilize unsupervised machine learning algorithms to identify subtypes of IPN based on clinical characteristics.