Dupuytren’s disease is a benign fibroproliferative disorder, characterized by a progressive retraction of the palmar fascia that leads to permanent digital flexion deformities, mainly at the fourth and fifth finger [1]. The disease is a complex process involving a cascade of molecular and cellular events, with TGF-b, bFGF and PDGF playing a pivotal role in fibroblasts proliferation and differentiation into myofibroblasts producing a characteristic extracellular matrix. In fact, palmar fascias of patients with Dupuytren’s contracture show a twofold concentration of byglican and sulfated GAG’s when compared to normal tissue, thus leading to a storage of Dermatan sulfate and Chondroitin sulfate similar to findings in hypertrofic skin scars [2]. Many drugs have been proposed to stop or decrease the cascade of events generated by the inappropriate production of TGF-b and other growth factors, as well as to stop the progression of disease in the early stages; these include imiquimod, interferon a-2b, collagenase and, recently, N-acetyl-Lcysteine [3]. Nonetheless, surgery represents the only available treatment to remove the pathological tissue, despite it is associated to complications such as finger flexion contracture for recurrence or scar contracture, neurological and vascular lesions and skin necrosis. MESNA (sodium-2-mercaptoethanesulfonate), is a mucolythic agent that disrupts disulfide bonds of the mucous polypeptide chains; it has been effective in dissolving connections between tissues by separation of collagen fibres, probably exerting an action on the disulfide bonds of the extracellular matrix polypeptide chains [4]. The drug has been used as a ‘‘chemical dissector’’ to ease in finding a surgical cleavage during surgical procedures of myomectomy, laparoscopic excision of endometriotic cysts and in the treatment of cholesteatoma and acustic neuromas [5]. MESNA can be the ideal candidate for clinical applications in Dupuytren’s disease; in fact, the action on disulfide bonds exerted by the molecule can be quintessential, provided the high content of sulphured GAG such as Dermatan Sulphate and Keratan Sulphate of palmar fascia of patients affected by Dupuytren’s disease.
Off-label use of MESNA in Dupuytren's disease
Di Martino, Alberto;
2008
Abstract
Dupuytren’s disease is a benign fibroproliferative disorder, characterized by a progressive retraction of the palmar fascia that leads to permanent digital flexion deformities, mainly at the fourth and fifth finger [1]. The disease is a complex process involving a cascade of molecular and cellular events, with TGF-b, bFGF and PDGF playing a pivotal role in fibroblasts proliferation and differentiation into myofibroblasts producing a characteristic extracellular matrix. In fact, palmar fascias of patients with Dupuytren’s contracture show a twofold concentration of byglican and sulfated GAG’s when compared to normal tissue, thus leading to a storage of Dermatan sulfate and Chondroitin sulfate similar to findings in hypertrofic skin scars [2]. Many drugs have been proposed to stop or decrease the cascade of events generated by the inappropriate production of TGF-b and other growth factors, as well as to stop the progression of disease in the early stages; these include imiquimod, interferon a-2b, collagenase and, recently, N-acetyl-Lcysteine [3]. Nonetheless, surgery represents the only available treatment to remove the pathological tissue, despite it is associated to complications such as finger flexion contracture for recurrence or scar contracture, neurological and vascular lesions and skin necrosis. MESNA (sodium-2-mercaptoethanesulfonate), is a mucolythic agent that disrupts disulfide bonds of the mucous polypeptide chains; it has been effective in dissolving connections between tissues by separation of collagen fibres, probably exerting an action on the disulfide bonds of the extracellular matrix polypeptide chains [4]. The drug has been used as a ‘‘chemical dissector’’ to ease in finding a surgical cleavage during surgical procedures of myomectomy, laparoscopic excision of endometriotic cysts and in the treatment of cholesteatoma and acustic neuromas [5]. MESNA can be the ideal candidate for clinical applications in Dupuytren’s disease; in fact, the action on disulfide bonds exerted by the molecule can be quintessential, provided the high content of sulphured GAG such as Dermatan Sulphate and Keratan Sulphate of palmar fascia of patients affected by Dupuytren’s disease.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
