No approved-drug candidate for polyneuropathy is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
RCSB Protein Data Bank · entry 8C86 · 1.1 Å · ligand (2,4-dimethylphenyl)(4-hydroxy-3-methoxy-5-nitrophenyl)methanone (TQ0). Experimental structure, not a prediction.
Charcot-Marie-Tooth polyneuropathy is a genetically and clinically heterogeneous group of disorders for which molecular understanding has advanced but no treatment has emerged from that understanding. A 1999 review noted that reclassification based on molecular mechanisms might eventually help find a way to control or treat these hereditary neuropathies, but no drug therapy was described.
A 2004 Cochrane review of drug therapy for chronic idiopathic axonal polyneuropathy identified 18 studies for possible inclusion and excluded all of them because of insufficient quality or lack of relevance. The review concluded that no adequate randomised or quasi-randomised controlled clinical treatment trials had been performed, and that in their absence there is no proven efficacious drug therapy.
A 2018 randomised open-label comparative effectiveness study in cryptogenic sensory polyneuropathy enrolled 402 patients and tested four drugs: nortriptyline, duloxetine, pregabalin, and mexiletine. The posterior probability that each treatment was best was 0.52 for nortriptyline, 0.43 for duloxetine, 0.05 for pregabalin, and 0.00 for mexiletine. Efficacy rates were 25.4% for nortriptyline, 23.0% for duloxetine, 15.1% for pregabalin, and 20.3% for mexiletine. Quit rates were 38.1%, 37.3%, 42.5%, and 58.0% respectively. Mexiletine met the criteria for being a loser primarily due to side effects. There was no clear winner; nortriptyline and duloxetine outperformed pregabalin and mexiletine.
A 2023 study of immune-mediated polyneuropathy in 45 patients and 46 controls found that transcript levels of CD137 and CD137L were higher in patients (P=0.006 for both), while serum sCD137 was significantly lower (P<0.001). The authors stated that more investigations are required to clarify the exact contributions of these molecules to pathogenesis. What is still missing for polyneuropathy as a whole is randomised controlled trial data for most subtypes, a clear biomarker to stratify patients by molecular mechanism, and funding for adequately powered comparative effectiveness studies that can identify which drug works for which patient.
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2003 · 369 citations
Venlafaxine versus imipramine in painful polyneuropathy
AbstractBACKGROUND: Tricyclic antidepressants (TCA) are often used in the treatment of painful polyneuropathy. Venlafaxine is a serotonin and weak noradrenaline reuptake inhibitor antidepressant with a different profile of other pharmacologic actions from those of TCA. OBJECTIVE: To test if venlafaxine would relieve painful polyneuropathy and compare its possible efficacy with that of the TCA imipramine. METHODS: The study design was randomized, double blind, and placebo controlled, with a three-way crossover. Forty patients were assigned to one of the treatment sequences, and 29 completed all three study periods. The daily doses were venlafaxine 225 mg and imipramine 150 mg. During the three treatment periods, each of 4 weeks' duration, patients rated pain paroxysms, constant pain, and touch- and pressure-evoked pain by use of 0- to 10-point numeric rating scales. RESULTS: The sum of the individual pain scores during treatment week 4 was lower on venlafaxine (80% of baseline score; p = 0.006) and imipramine (77%; p = 0.001) than on placebo (100%) and did not show any statistical difference between venlafaxine and imipramine (p = 0.44). The individual pain scores for pain paroxysms, constant pain, and pressure-evoked pain showed a similar pattern, whereas touch-evoked pain was uncommon and was not altered by any of the drugs. Numbers needed to treat to obtain one patient with moderate or better pain relief were 5.2 for venlafaxine and 2.7 for imipramine. CONCLUSION: Venlafaxine relieves pain in polyneuropathy and may be as effective as imipramine.
https://doi.org/10.1212/01.wnl.0000058749.49264.bdAnnals of the New York Academy of Sciences · 1999 · 43 citations
A Clinical Review of Charcot‐Marie‐Tooth
AbstractCMT polyneuropathy is a complex genetically and clinically heterogeneous group of disorders. The rapid advances in our understanding of the molecular basis of these groups of neuropathies have helped to resolve some of the controversial issues regarding the clinical and genetic classification. However, there is still confusion and chaos in the terminology employed by different groups of researchers. A reclassification based on the molecular mechanisms of these neuropathies will help in the future to unify and simplify the diagnosis of these complex disorders. The understanding of the molecular mechanisms will also help in the future to find a way to control or treat these hereditary neuropathies.
https://doi.org/10.1111/j.1749-6632.1999.tb08570.xArchives of Neurology · 2011 · 22 citations · open access
The Evaluation of Distal Symmetric Polyneuropathy
AbstractOBJECTIVE: To define current clinical practice for evaluating distal symmetric polyneuropathy. DESIGN: Using a modified Dillman method, we sent surveys to 600 internists, 600 neurologists, and 45 neuromuscular specialists selected from the American Medical Association Physician Masterfile. Survey questions pertained to which tests providers would order in the following 3 scenarios: (1) the initial evaluation of distal symmetric polyneuropathy, (2) the use of additional tests if the initial evaluation was unrevealing, and (3) patients with diabetes. The t test was used to compare the number of tests ordered by physician type, and the χ(2) test was used to compare proportions of tests ordered. SETTING: National survey of physicians. PARTICIPANTS: Internists, neurologists, and neuromuscular specialists. RESULTS: The response rate was 35%. Overall, many tests were ordered for the full evaluation of distal symmetric polyneuropathy (mean [SD], 16.5 [7.2] tests), and there was substantial variation within and between provider types. Internists ordered fewer tests (mean [SD], 14.5 [6.1] tests) than did neurologists (mean [SD], 17.5 [7.9] tests) (P < .001). Regarding the glucose tolerance test, substantial differences were found between physician types, with neurologists and neuromuscular specialists ordering this test more frequently (28.6% and 72.3%, respectively) and internists ordering it less frequently (4.1%). A brain and/or spine magnetic resonance imaging scan was ordered by 19.8% of internists and 12.9% of neurologists. CONCLUSIONS: From the supporting evidence, current practice intent on evaluating distal symmetric polyneuropathy is highly variable and differs widely. For this disorder of the peripheral nerves, a high-yield test such as the glucose tolerance test is rarely used, whereas magnetic resonance imaging is likely overused. Research that defines the optimal evaluation of distal symmetric polyneuropathy has the potential to result in more efficient care.
https://doi.org/10.1001/archneurol.2011.1735Disability and Rehabilitation · 2009 · 20 citations
Polyneuropathy, with and without neurogenic pain, and its impact on daily life activities – A descriptive study
AbstractPURPOSE: Few studies on disabilities relate to neurogenic chronic pain conditions and how pain influences the patient's ability to maintain life roles. Polyneuropathy is a condition with muscle weakness, sensory impairment and sometimes additional pain of neurogenic origin. The aim was to investigate disability reported in daily activities and quality of life in patients with polyneuropathy, with and without neurogenic pain. METHOD: A mail questionnaire designed to collect data on the state of health and impact on daily activities, including the Quality of Life-scale, Swedish version (QOLS-S), were sent to 60 patients with polyneuropathy. Forty-two (72.4%) responded. RESULTS: Twenty-three patients were old-age pensioners (>65 years), ten had disability pension and nine were employed. Twenty-seven patients reported pain in addition to polyneuropathy. The neuropathy symptoms influenced occupational performance at work and leisure and in housework for 72% of the patients. Patients with additional neurogenic pain reported significantly greater performance problems in 55% of the daily activities compared with patients without pain. Quality of life was significantly lower for patients with pain concerning health and participation in active recreation. CONCLUSIONS: Symptoms in polyneuropathy, especially when accompanied by pain, give rise to disability that affects daily activities and ought to be considered in planning a successful intervention programme.
https://doi.org/10.1080/09638280802621382Cochrane Database of Systematic Reviews · 2004 · 9 citations
Drug therapy for chronic idiopathic axonal polyneuropathy
AbstractBACKGROUND: Chronic idiopathic axonal polyneuropathy is an insidiously progressive sensory or sensorimotor polyneuropathy that affects elderly people. Although severe disability or handicap does not occur, it reduces quality of life. OBJECTIVES: To assess whether drug therapy for chronic idiopathic axonal polyneuropathy reduces disability, ameliorates neurological symptoms and associated impairments, and whether treatment is safe. SEARCH STRATEGY: We searched Cochrane Library (Cochrane Neuromuscular Disease Review Group Register, Cochrane Database of Systematic Reviews, Cochrane Database of Abstracts of Reviews of Effectiveness, and the Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE, ISI, and ACP Journal Club's Best Evidence, from 1981 until December 2002. We also hand searched the reference lists of relevant articles, reviews and textbooks identified electronically, and contacted authors and other experts in the field to identify additional studies. SELECTION CRITERIA: We sought all randomised or quasi-randomised (alternate or other systematic treatment allocation), unconfounded trials that examined the effects of any drug therapy in patients with chronic idiopathic axonal polyneuropathy at least one year after the onset of treatment. Patients with chronic idiopathic axonal polyneuropathy had to fulfil the following criteria: age 40 years or older, distal sensory or sensorimotor polyneuropathy, absence of systemic or other neurological disease, chronic clinical course not reaching a nadir in less than two months, exclusion of any recognised cause of the polyneuropathy by medical history taking, clinical or laboratory investigations, electrophysiological studies in agreement with axonal polyneuropathy without evidence of demyelinating features. The primary outcome was the proportion of patients with a significant improvement in disability. Secondary outcomes were change in the mean disability score, change in the proportion of patients who make use of walking aids, change in the mean Medical Research Council sum score, degree of pain relief and/or reduction of other positive sensory symptoms, change in the proportion of patients with pain or other positive sensory symptoms, and frequency of adverse effects. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed and extracted details of trial methodology and outcome data of all potentially relevant trials. MAIN RESULTS: Eighteen studies were identified and assessed for possible inclusion in the review, but all were excluded because of insufficient quality or lack of relevance. REVIEWERS' CONCLUSIONS: Even though chronic idiopathic axonal polyneuropathy has been clearly described and delineated, no adequate randomised or quasi-randomised controlled clinical treatment trials have been performed. In their absence there is no proven efficacious drug therapy.
https://doi.org/10.1002/14651858.cd003456.pub2Neurology · 2018 · 4 citations
Patient Assisted Intervention for Neuropathy: Comparison of treatment in real life situations (PAIN-CONTRoLS) (P1.435)
AbstractObjective: To determine which of the 4 pharmaceutical therapies (pregabalin, duloxetine, nortriptyline or mexiletine) is most effective for neuropathic pain and best tolerated in cryptogenic sensory polyneuropathy (CSPN). Background: CSPN is a common slowly progressive neuropathy that affects adults and presents with significant neuropathic pain for which multiple medications have been tried including antiepileptics, antidepressants, topicals and narcotics. A web based survey among neuromuscular experts suggested pregabalin as being more effective than other medications, however there are presently no comparative studies to assess the most effective medication. Design/Methods: We performed a prospective randomized open labelled comparative effectiveness study of CSPN patients through the Patient Centered Outcomes Research Institute (PCORI). The study used a Bayesian adaptive design, which included response adaptive randomization. At each interim analysis a decision was made to either continue enrolling patients or to stop the trial for success. CSPN patients who fulfilled the inclusion and exclusion criteria were enrolled into this study. Patients underwent a baseline neurological evaluation and randomly assigned to one of the 4 neuropathic medications for 12 weeks. The co-primary outcomes are the change in likert-like pain scale and quit rates. The outcome measures were performed at baseline, week 4, 8 and 12. Results: There were a total of 402 CSPN patients with 134, 126, 73, and 69 randomized to nortriptyline, duloxetine, pregabalin, and mexiletine, respectively. The posterior probability each treatment was best were 0.52, 0.43, 0.05, and 0.00, with efficacy rates 25.4%, 23.0%, 15.1%, 20.3% and quit rates of 38.1%, 37.3%, 42.5%, 58.0%, respectively. Conclusions: Mexiletine met our criteria for being a loser, primarily due to side effects. While there was no clear winner, overall nortriptyline and duloxetine outperformed pregabalin and mexiletine. Study Supported by: PCORI: Grant Number: CER-1306-02496 Disclosure: Dr. Barohn has nothing to disclose. Dr. Gajewski has nothing to disclose. Dr Pasnoor has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Herbelin has nothing to disclose. Dr. Kimminau has nothing to disclose. Dr. Jawdat has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Parks has nothing to disclose. Dr. Shlemon has nothing to disclose. Dr. Dimachkie has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dr. Dimachkie is on the speaker’s bureau or is a consultant for Baxalta, Catalyst, CSL Behring, Mallinckrodt, Novartis and NuFactor. He has received grants from Alexion, Biomarin, Catalyst, CSL-Behring, FDA/OPD, GSK, MDA, NIH, Novartis, Orphazyme and TM. Dr. Study Team has nothing to disclose.
https://doi.org/10.1212/wnl.90.15_supplement.p1.435PubMed · 2023 · 1 citations · open access
Evaluation of CD137 and CD137L Transcript Levels and the Serum sCD137 in Immune-mediated Polyneuropathy.
AbstractBackground: Abnormal humoral and cellular immune responses have been reported in immune-mediated polyneuropathies. CD137, as a costimulatory molecule and a TNF receptor superfamily member, has been demonstrated to have a key role in the pathogenesis of many autoimmune as well as inflammatory disorders. Objective: To evaluate the transcripts levels of CD137, its ligand (CD137L), and the serum levels of soluble CD137 (sCD137) in patients with immune-mediated polyneuropathy. Methods: A total of 45 patients and 46 sex and age-matched healthy individuals were enrolled in the study. CD137 and CD137L transcript levels were assessed by the Real-Time PCR, and the serum level of sCD137 was measured using the ELISA technique. The Bayesian regression model was used for statistical analysis at the 0.05 significance level in R 4.1.0 statistical environment. Results: Transcript levels of the CD137 and CD137L were higher in polyneuropathy patients in comparison with the healthy subjects (P=0.006 for both). Conversely, the mean level of sCD137 was significantly lower in the sera of patients compared to the controls (P<0.001). Conclusion: Our findings point to the possible role of CD137 and CD137L in immune-mediated polyneuropathy pathogenesis. More investigations are required to clarify the exact contributions of the mentioned molecules to the pathogenesis of immune-mediated polyneuropathies.
https://doi.org/10.22034/iji.2023.96695.2453Fortschritte der Neurologie · Psychiatrie · 1998 · 1 citations
Polyneuropathien unter Lösungsmitteleinwirkung
AbstractPolyneuropathy is a clinically diagnosed disorder. The diagnostic features consist mainly of subjective complaints about distally marked paresthesia or dysaesthesia, pain and motor disturbances like cramps. Neurological examination typically shows weak or absent tendon reflexes (early signs: weak or absent Achilles tendon reflexes), distally marked disturbances of sensitivity (early sign: reduced sense of vibration), atrophic paresis, cranial nerve impairment and disturbances of the autonomic nervous system. Results of additionally performed electrophysiological examinations (nerve conduction studies, vibratometry and thermotesting) contribute to the diagnosis. Polyneuropathy is undoubtedly induced by carbon disulfite, ethylene glycol, n-hexane and methyl-n-butylketone, triorthocresyl phosphate and solvent mixtures. Induction of polyneuropathy is doubtful with the following substances: tetrachloride, trichlorethylene, styrene, toluene. Additional impairment of the central nervous system is often indicated by clinical findings of brisk patellar tendon reflexes or the occurrence of Babinski's sign.
https://doi.org/10.1055/s-2007-995296Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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