A call to action for peripheral neuropathy research funding—Time to consolidate funding under one NIH initiative?

Journal of the Peripheral Nervous System, Год журнала: 2025, Номер 30(1)

Опубликована: Янв. 12, 2025

Peripheral neuropathies (PNs) pose a significant clinical challenge in the field of neurological disorders, with prevalence 2.4% general population that rises age to over 8% patients aged 55 years and older.1 Symmetrical, distal-to-proximal axonal loss is most common form PN accounts for cases.2, 3 It characterized by damage peripheral nerves typically, especially diabetes (the leading cause PN), impacts small-diameter axons beginning feet progresses proximally length-dependent manner. results range debilitating symptoms such as numbness, tingling, weakness, well burning or shooting pain.4 Along these painful symptoms, may experience depression, anxiety, sleep disturbances.5 As progresses, individuals present diminished sensation mechanical thermal stimuli, making it challenging perceive effectively heal injuries trauma, which increases risk non-healing ulcers. In severe cases, cumulative effects ulcers can necessitate lower limb amputations.6 fact, are almost four times at greater undergoing lower-limb amputation than those without.7 Additionally, also leads an increased falls due compromised balance proprioception, further exacerbating potential injury disability affected individuals. likely far more tissues organs previously appreciated.8 Data now indicate diabetic exists muscle, liver, adipose tissue, pancreas, gastrointestinal tract, heart.9-17 profoundly lives patients, limited therapeutic options mitigate pain prevent progression, regenerate lost axons. While presentations appear similar, result from causes, including both inherited acquired conditions. Hereditary (HN), Charcot–Marie-Tooth (CMT) disease hereditary sensory autonomic neuropathies, comprise diverse group overall 1:2500.18 These differ their inheritance patterns (autosomal dominant, recessive, X-linked), electrophysiological characteristics (demyelinating, axonal, intermediate), features. not other types, HN highlight importance genetic factors neuropathic disorders. Of neuropathy (DPN) prevalent, accounting 32%–53% total cases.2 cases expected rise 537 783 million 2045, DPN, affects 50% frequency duration, will increase.19 Importantly, Global Burden Disease Study 2021 ranked DPN among top 10 causes ill health worldwide.20 Chemotherapy-induced (CIPN) side effect chemotherapeutic agents, affecting roughly half cancer treatments,21 lead dose reduction premature cessation chemotherapy, thus impeding treatment efficacy worsening outcomes.22 persist about one-third survivors after cessation, severely quality life.22 Inflammatory observed autoimmune conditions like Guillain-Barré syndrome, arise when immune system directly attacks damages nerve fibers, causing degeneration, demyelination, subsequent motor impairments.23 Infectious on hand, direct infection inflammatory responses triggered pathogens human immunodeficiency virus, leprosy, COVID-19. infections through mechanisms viral replication within nerves, immune-mediated attacks, production neurotoxic substances. note, associated long COVID represents growing patient wealth data regarding dysfunction.24 Finally, be categorized idiopathic, no known underlying cause, manifest alongside natural aging process. Beyond its implications, poses economic societal burden, encompassing medical indirect social costs, addition decreased life individuals.25 For example, 2003, estimated annual healthcare costs complications were between 4.6 13.7 billion USD, while cost managing syndrome 2004 was 1.7 USD.26, 27 Likewise, average CIPN $17 344 higher without.28 estimates have been updated underrepresent current costs. The financial implications extend visits, hospitalizations, specialized care.29 Moreover, PN, acquired, long-term disability, reduced workforce participation. Employed miss 5.5 workdays per month30 reliance support systems. emotional toll living chronic impact mental interpersonal relationships, burden condition.31 ages cancer, continues rise, understanding identifying effective remains unmet public need. Inherited etiology. They do, however, share similar damage, myelin abnormalities, cell activation, point overlapping molecular provide insights across etiologies. NIH-funded studies revealed oxidative stress inflammation established key players all conditions.4, 32, 33 More recently, guided our precise role abnormal mitochondrial dynamics CIPN.34, 35 we know axon stability regulated non-cell autonomous mechanisms, involve metabolic communication Schwann cells.4 Consequently, believe supporting basic foundational research whole crucial, pathogenic one subtype valuable clues treating subtypes. development gene therapies transthyretin (TTR) rapid evolvement sorbitol dehydrogenase (SORD) deficiency trials this disease, targeted next-generation sequencing panels improved CMT diagnosis each how discoveries translate tangible advancements care. focus has shifted investigating single exploring biological systems using omics-based approaches genomics single-cell transcriptomics. potentially uncover unrecognized targets thereby enhance whole.4 Therefore, contend prioritizing shared via advanced techniques omics methodologies microscopy, inform towards underscoring investigations collaborative effort institutes National Institutes Health (NIH). difficult overstate. However, United States, NIH allocates funding institutes, dedicated specific area research. result, fragmented, different types receiving separate institutes: primarily funded Institute Diabetes Digestive Kidney Diseases (NIDDK), Cancer (NCI), aging-related Aging (NIA), Neurological Disorders Stroke (NINDS; Table 1). siloed approach led important scientific pathogenesis intervention, described above, hinders collaboration information-sharing researchers under-values target degeneration versus overall, consider distinct highly morbid disorder worthy own mechanistic even beyond (or restricted) individual limitations structure perpetuate lack slow identification disease-modifying therapies. By comparison, Europe's structure, European Union Horizon Europe (2021–2027),36 adopts comprehensive, cross-disciplinary strategy. emphasizes extensive, projects engage various stakeholders prioritize critical pathological areas based parameters impact, innovation, PN. This offers numerous advantages information sharing Centralizing coordination PN-related would streamline researchers, allowing exchange knowledge, data, resources disciplines. pooling expertise under cross-institute initiative, could foster innovative targeting pathways A successful example type Pain Consortium, NINDS, brought together multiple address comprehensively, encouraging multidisciplinary resource increasing visibility Similarly, NINDS NIA Alzheimer's Disease–Related Dementias (AD/ADRD) highlights effectiveness integrated establishing priorities advancing complex prevalent AD/ADRD,20 highlighting need unified efforts. models serve templates proposed initiative. Overall, consolidating partnership program strategic efficient knowledge improving outcomes many letter proposes operational model community promote decision-makers. Funding provided (P30DK020572 K01DK135799 S.A.E.; R01DK130913 R24DK082841 E.L.F.); Novo Nordisk Foundation (NNF14OC0011633 E.L.F.), Nathan Rose Milstein Research Fund (to S.A.E.), Sinai Medical Staff Robert Katherine Jacobs Environmental Initiative Andrea Lawrence Wolfe Brain E.J.K. Dr. John H. Doran Neuropathy S.A.E. E.L.F), NeuroNetwork Emerging Therapies University Michigan E.L.F.). K.L.T. co-founder CSO Neuright, Inc. All authors relevant conflicts disclose. applicable article datasets generated analysed during study.

Язык: Английский

Transdermal electrophysiological recordings of diet-induced small fiber peripheral neuropathy using a needle electrode array in mice and man

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Янв. 10, 2025

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Proactive treatment options remain limited, which exacerbated by lack sensitive and convenient diagnostics, especially early in disease progression or specifically to assess small fiber (SFN), the loss distal diameter axons that innervate tissues organs. We designed, fabricated, tested, validated first-of-its-kind medical diagnostic device for functional assessment transdermal nerve activity. This device, Detecting Early Neuropathy (DEN), an electrically conductive needle array designed record electrical activity skin subdermal tissues, as feature broader theragnostic platform. DEN recordings were across time course diet-induced PN mice, using statistical computational analyses compared other SFN measures. Based on these preclinical mouse data, design was adapted obtain human with flexible printed circuit board mold leg regions. The successfully recorded various types neural human, without stimulation, including action potentials electromyography signals. New tools like offer promising outlook patients needing earlier more diagnosis DPN/SFN, allow effective options, become available clinic future years.

Язык: Английский

Feasibility of trancutaneous auricular vagus nerve stimulation in Black and Hispanic/Latino people with peripheral neuropathy

Frontiers in Pain Research, Год журнала: 2025, Номер 5

Опубликована: Янв. 17, 2025

Peripheral neuropathy (PN) is the most common neurodegenerative disorder, and primary causes are chemotherapy-induced peripheral (CIPN) diabetic (DN). Transcutaneous auricular vagus nerve stimulation (taVNS) a promising non-pharmacological non-invasive intervention that targets key pathways involved with PN. However, research needed to determine feasibility, acceptability, effects of taVNS in people It also critical this on include perspectives Black Hispanic/Latino patients, who often underrepresented research. This was comprised two consecutive studies: survey pilot randomized sham-controlled trial (RCT). The assessed symptom burden, management strategies, interest among CIPN patients. RCT evaluated preliminary patients or neuropathy. Participants were recruited from University Miami medical system, culturally sensitive approaches enhance minority participation. included 62 respondents, 78% Hispanic/Latino, revealing high burden significant (82% expressed moderate interest). enrolled 28 participants, achieving 42% recruitment rate 86% retention. well tolerated, no adverse effects. Preliminary data indicated decrease neuropathic symptoms an increased heart variability (HRV) during active taVNS, suggesting autonomic modulation. Tingling sensation pain decreased by median values 2.0 1.5, respectively. Additionally, for standard deviation RR interval 34.9 (CI = 21.6-44.8) at baseline 44.8 26.5-50.3) intervention. Exit interviews highlighted positive participant experiences identified potential barriers, such as protocol length distrust findings underscore need novel treatments demonstrate feasibility conducting historically populations. High successful retention rates suggest can participation clinical trials. These will be used develop large efficacy repeated diverse cohort. https://clinicaltrials.gov, identifier (NCT05896202).

Язык: Английский