PNRR Data Ongoing Projects | Summary Sheet
A. Research Projects for which serum, plasma and/or DNA was provided together with data:
1.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.
2. 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.
3. 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.
4. 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.
5. Johns Hopkins / Washington University (2019 – planned):
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 Hoke (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 will be distributed to Washington University to further the research.
B. Data Analysis Projects:
6. 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.
7. Johns Hopkins University (2019 – ongoing):
a. Student Project: “Effects of height and age on sural responses”- evaluation of measured sural sensory nerve responses in correlation to height and age of the patients and also to evaluate for any other factors causing sensory nerve damage in the lower legs.
b. 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.
c. Student Project: “Exercise as an effective countermeasure to painful polyneuropathies.” Exercise information was collected on 450 patients enrolled at Johns Hopkins, the symptoms and severities of PN will be evaluated for different exercise patterns including frequency, type of exercise, duration of workout, etc.).
d. Resident Project: “Characteristics of large fiber versus small fiber idiopathic PN in a large cohort study.” Initial data analysis done on Johns Hopkins records only, secondary data analysis will include all idiopathic patients enrolled in PNRR.