Homozygous NMNAT2 mutation in sisters with polyneuropathy and erythromelalgia

Huppke, Peter; Wegener, Eike; Gilley, Jonathan; Angeletti, Carlo Alberto; Kurth, Ingo; Drenth, Joost P.H.; Stadelmann, Christine; Barrantes‐Freer, Alonso; Brück, Wolfgang; Thiele, Holger; Nürnberg, Peter; Gärtner, Jutta; Orsomando, Giuseppe; Coleman, Michael P.

doi:10.1016/j.expneurol.2019.112958

Cited by 54 publications

(50 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Efforts have been made to boost the function and increase the expression of nicotinamide nucleotide adenylyltransferase 2 (NMNAT2). Targeting the degradation of NMNAT2 might also be an alternative for neuropathy [114][115][116].…”

Section: Future Outlook: Data From Preclinical Studiesmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy—part 2: focus on the prevention of oxaliplatin-induced neurotoxicity

Sałat

2020

Pharmacol. Rep

View full text Add to dashboard Cite

Background Chemotherapy-induced peripheral neuropathy (CIPN) is regarded as one of the most common dose-limiting adverse effects of several chemotherapeutic agents, such as platinum derivatives (oxaliplatin and cisplatin), taxanes, vinca alkaloids and bortezomib. CIPN affects more than 60% of patients receiving anticancer therapy and although it is a nonfatal condition, it significantly worsens patients' quality of life. The number of analgesic drugs used to relieve pain symptoms in CIPN is very limited and their efficacy in CIPN is significantly lower than that observed in other neuropathic pain types. Importantly, there are currently no recommended options for effective prevention of CIPN, and strong evidence for the utility and clinical efficacy of some previously tested preventive therapies is still limited. Methods The present article is the second one in the two-part series of review articles focused on CIPN. It summarizes the most recent advances in the field of studies on CIPN caused by oxaliplatin, the third-generation platinum-based antitumor drug used to treat colorectal cancer. Pharmacological properties of oxaliplatin, genetic, molecular and clinical features of oxaliplatin-induced neuropathy are discussed. Results Available therapies, as well as results from clinical trials assessing drug candidates for the prevention of oxaliplatininduced neuropathy are summarized. Conclusion Emerging novel chemical structures-potential future preventative pharmacotherapies for CIPN caused by oxaliplatin are reported.

show abstract

Section: Future Outlook: Data From Preclinical Studiesmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy—part 2: focus on the prevention of oxaliplatin-induced neurotoxicity

Sałat

2020

Pharmacol. Rep

View full text Add to dashboard Cite

show abstract

“…[1,4]. In 2019, 14 EM cases have been reported in the literature despite the high probability of missed diagnosis and non-reported cases [5][6][7][8][9][10][11][12][13][14][15][16][17].…”

Section: Discussionmentioning

confidence: 99%

“…It is very likely that the role of SCN9 family of genes is only cumulative to a yet unidentified constellation of mutations [10,13], necessitating further research in exploring mutations unique to the skin vasculature. Given unexplained risk of development of MPO secondary to EM, we should also consider JAK2 mutations in primary disease pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

“…Topical formulations like amitriptyline-ketamine, lidocaine, capsaicin, midodrine and neuronal calcium channels modulators like gabapentin have also been used [3,12]. Decreased pain perception through targeted Nav1.7 channel antagonism is still experimental whereas mutant potassium channels antagonism and NAD synthesizing mutant NMNAT2 enzyme potentiation is yet unexplored [13,32,35]. So far, we have been unable to market an effective and safe EM specific pharmacologic therapy.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Primary Erythromelalgia Complicated by Cellulitis: A Case Report and Review of Literature

Sharif¹,

Haider²,

Freeman³

et al. 2020

AJMCR

View full text Add to dashboard Cite

Background: Erythromelalgia is a rare disease with increasing incidence. It manifests as episodic painful red extremities triggered by heat. External cooling provides temporary symptomatic relief but may lead to complications such as cellulitis. Management includes trigger control, behavioral therapy and pain management. Case Presentation: A 47-year-old African American male presented to the hospital with worsening bilateral lower extremity pain for three months. It was episodic, triggered by running and associated with erythema and swelling. Patient used cold water immersion and air conditioning for pain relief. One week prior to presentation, he developed painful blisters on his feet. On presentation, vital signs were stable, patient was afebrile. Acute infection was ruled out and he was discharged with outpatient rheumatology follow up for erythromelalgia. He returned one week later with worsening symptoms. CT scan of lower extremities indicated bilateral cellulitis. Patient was managed by medicine, dermatology, rheumatology, and podiatry for cellulitis, fungal infection, trench foot and primary erythromelalgia with antibiotics, antifungals, gabapentinoids and behavioral therapy. His infection resolved and pain improved. He was discharged with outpatient rheumatology follow up. Discussion: Erythromelalgia is a highly debilitating disease with episodes of burning erythematous extremities triggered by increase in skin temperature. Patients seek pain relief by excessive external cooling. Pathophysiology involves gain of function mutation in voltage gated sodium channels causing autoregulatory dysfunction of skin. Underlying disease mechanisms are ambiguous and may involve unidentified genetic components and unknown triggers. It is a clinical diagnosis. Therapy requires a multidisciplinary approach. Complications should be promptly addressed given attention next to symptomatic relief. There is a lack of disease specific treatment and complete remission is unlikely. Our patient responded well to gabapentinoids and behavioral therapy.

show abstract

“…Mutations in human Nmnat2 have been linked to fetal akinesia deformation sequence (FADS), and to childhood-onset polyneuropathy and erythromelalgia [109,110]. These discoveries provide the first direct molecular evidence that axon death in WD is involved in a human axonal disorder.…”

Section: Axon Death Signalling In Diseasementioning

confidence: 99%

Axon death signalling in Wallerian degeneration among species and in disease

Rosell

Neukomm

2019

Open Biol.

View full text Add to dashboard Cite

Axon loss is a shared feature of nervous systems being challenged in neurological disease, by chemotherapy or mechanical force. Axons take up the vast majority of the neuronal volume, thus numerous axonal intrinsic and glial extrinsic support mechanisms have evolved to promote lifelong axonal survival. Impaired support leads to axon degeneration, yet underlying intrinsic signalling cascades actively promoting the disassembly of axons remain poorly understood in any context, making the development to attenuate axon degeneration challenging. Wallerian degeneration serves as a simple model to study how axons undergo injury-induced axon degeneration (axon death). Severed axons actively execute their own destruction through an evolutionarily conserved axon death signalling cascade. This pathway is also activated in the absence of injury in diseased and challenged nervous systems. Gaining insights into mechanisms underlying axon death signalling could therefore help to define targets to block axon loss. Herein, we summarize features of axon death at the molecular and subcellular level. Recently identified and characterized mediators of axon death signalling are comprehensively discussed in detail, and commonalities and differences across species highlighted. We conclude with a summary of engaged axon death signalling in humans and animal models of neurological conditions. Thus, gaining mechanistic insights into axon death signalling broadens our understanding beyond a simple injury model. It harbours the potential to define targets for therapeutic intervention in a broad range of human axonopathies.

show abstract

Homozygous NMNAT2 mutation in sisters with polyneuropathy and erythromelalgia

Cited by 54 publications

References 32 publications

Chemotherapy-induced peripheral neuropathy—part 2: focus on the prevention of oxaliplatin-induced neurotoxicity

Chemotherapy-induced peripheral neuropathy—part 2: focus on the prevention of oxaliplatin-induced neurotoxicity

Primary Erythromelalgia Complicated by Cellulitis: A Case Report and Review of Literature

Axon death signalling in Wallerian degeneration among species and in disease

Contact Info

Product

Resources

About