Bosentan: A novel therapy for leg ulcers in Werner syndrome

Noda, Shinichi; Asano, Yoshihide; Masuda, Sho; Miyagawa, Takuya; Sugita, Masaaki; Yamamoto, Mizuho; Kogure, Asako; Tamaki, Zenshiro; Mitsui, Hiroshi; Hoashi, Toshihiko; Sugaya, Makoto; Sato, Shinichi

doi:10.1016/j.jaad.2011.03.013

Cited by 11 publications

(6 citation statements)

References 7 publications

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“…Honjo et al have reported that administration of sodium etidronate led to the improvement of painful soft-tissue calcification in patients with WS [14]. Noda et al also suggested that bosentan (Tracleer ® , Actelion Pharmaceuticals), which is a dual endothelin receptor antagonist, could be a promising treatment option for intractable cutaneous ulcers in WS [15]. Walton et al reported number of complications after surgical procedures in patients with WS, probably due to the lack of bone healing and soft-tissue repair in these patients [9].…”

Section: Clinical Backgroundmentioning

confidence: 99%

Radiographic presentation of musculoskeletal involvement in Werner syndrome (adult progeria)

David

Vincent

Arrigoni

et al. 2017

Diagnostic and Interventional Imaging

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Werner syndrome (i.e., adult progeria) is a rare autosomal recessive disorder caused by mutations of the WRN gene, which is characterized by the premature appearance of features associated with normal aging and cancer predisposition. Patients with Werner syndrome can present with musculoskeletal complaints, associated with suggestive radiographic features with a potential prognostic or therapeutic impact. This review illustrates the main radiographic features of Werner syndrome, focusing on the musculoskeletal system, such as soft-tissue calcification, muscular atrophy, osteoporosis, foot deformities, osteitis and osteomyelitis, and bone or soft-tissues malignancies. The identification of these features by radiologists can therefore be useful in the clinical screening of Werner syndrome.

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Section: Clinical Backgroundmentioning

confidence: 99%

Radiographic presentation of musculoskeletal involvement in Werner syndrome (adult progeria)

David

Vincent

Arrigoni

et al. 2017

Diagnostic and Interventional Imaging

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“…Severe ulcers are commonly found in heels, ankles, elbows, and other areas subject to pressure, and can be surgically treated in some cases only ( Yeong and Yang, 2004 ). However, drug therapy including basic fibroblast growth factor spray, hydrocolloid dressing, and PGE1 preparation have little effect on the ulcers in WS, although it is reported that topical platelet-derived growth factor-BB and the endothelin receptor antagonist bosentan has shown some beneficial effects ( Wollina et al, 2004 ; Noda et al, 2011 ). Most deep and severe leg ulcers with necrosis require amputations ( Yeong and Yang, 2004 ; Goto et al, 2013 ).…”

Section: Increased Longevity and Qol In Ws Patientsmentioning

confidence: 99%

Werner Syndrome-specific induced pluripotent stem cells: recovery of telomere function by reprogramming

2015

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Werner syndrome (WS) is a rare human autosomal recessive premature aging disorder characterized by early onset of aging-associated diseases, chromosomal instability, and cancer predisposition. The function of the DNA helicase encoded by WRN, the gene responsible for WS, has been studied extensively. WRN helicase is involved in the maintenance of chromosome integrity through DNA replication, repair, and recombination by interacting with a variety of proteins associated with DNA repair and telomere maintenance. The accelerated aging associated with WS is reportedly caused by telomere dysfunction, and the underlying mechanism of the disease is yet to be elucidated. Although it was reported that the life expectancy for patients with WS has improved over the last two decades, definitive therapy for these patients has not seen much development. Severe symptoms of the disease, such as leg ulcers, cause a significant decline in the quality of life in patients with WS. Therefore, the establishment of new therapeutic strategies for the disease is of utmost importance. Induced pluripotent stem cells (iPSCs) can be established by the introduction of several pluripotency genes, including Oct3/4, Sox2, Klf4, and c-myc into differentiated cells. iPSCs have the potential to differentiate into a variety of cell types that constitute the human body, and possess infinite proliferative capacity. Recent studies have reported the generation of iPSCs from the cells of patients with WS, and they have concluded that reprogramming represses premature senescence phenotypes in these cells. In this review, we summarize the findings of WS patient-specific iPSCs (WS iPSCs) and focus on the roles of telomere and telomerase in the maintenance of these cells. Finally, we discuss the potential use of WS iPSCs for clinical applications.

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“…However, topical PDGF‐BB results in limited healing of leg ulcers in Werner syndrome patients . In a case report, Bosentan, an endothelin receptor agonist, was reported to be effective for the treatment of severe skin ulcers in Werner syndrome patients . Because it is imperative to prevent infections in leg ulcers associated with Werner syndrome during the long treatment period, we hypothesized that both wound healing and antimicrobial actions might be effective for the treatment of severe leg ulcers.…”

Section: Discussionmentioning

confidence: 99%

Investigator‐initiated clinical study of a functional peptide, SR‐0379, for limb ulcers of patients with Werner syndrome as a pilot study

Nakagami

Sugimoto

Ishikawa

et al. 2019

Geriatrics Gerontology Int

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Aim An investigator‐initiated clinical study was carried out to evaluate the therapeutic potency of SR‐0379 for the treatment of leg ulcers in patients with Werner syndrome. Methods A multicenter, open‐label study was carried out from September 2017 to February 2018. The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia/venous stasis; and (ii) a wound size of >1 cm and <6 cm in diameter. Four individuals with Werner syndrome and diabetic ulcers, respectively, were enrolled. SR‐0379 (0.1%) was sprayed on skin ulcers once per day for 4 weeks. Efficacy was evaluated by determining the rate of wound size reduction as a primary end‐point at 4 weeks after the first treatment compared with the pretreatment wound size. As secondary end‐points, the DESIGN‐R score index, the 50% wound size reduction ratio, time to wound closure and quantification of wound bacteria were also evaluated. The safety of SR‐0379 was evaluated during the study period. Results The reduction rate of ulcer size treated with 0.1% SR‐0379 was 22.90% (mean) in the Werner syndrome ulcers group (n = 4) and 35.70% (mean) in the diabetic ulcers group (n = 4), respectively. The DESIGN‐R score decreased by 4.0 points in the Werner syndrome ulcers group and 4.3 points in the diabetic ulcers group. Two mild adverse events were reported in two patients, and causal relationships were denied in any events. Conclusion Treatment with SR‐0379 was safe, well‐tolerated, and effective for leg ulcers of both Werner syndrome and diabetes patients. Geriatr Gerontol Int 2019; 19: 1118–1123.

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Bosentan: A novel therapy for leg ulcers in Werner syndrome

Cited by 11 publications

References 7 publications

Radiographic presentation of musculoskeletal involvement in Werner syndrome (adult progeria)

Radiographic presentation of musculoskeletal involvement in Werner syndrome (adult progeria)

Werner Syndrome-specific induced pluripotent stem cells: recovery of telomere function by reprogramming

Investigator‐initiated clinical study of a functional peptide, SR‐0379, for limb ulcers of patients with Werner syndrome as a pilot study

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