Cystinosis: a new perspective

Abstract

Cystinosis is a rare, autosomal recessive inherited lysosomal storage disease. It is the most frequent and potentially treatable cause of the inherited renal Fanconi syndrome. If left untreated, renal function rapidly deteriorates towards end-stage renal disease by the end of the first decade of life. Due to its rarity and non-specific presentation, the entity is often not promptly recognized resulting in delayed diagnosis. Two major milestones in cystinosis management, cystine-depleting therapy with cysteamine and renal allograft transplantation, have had a considerable impact on the natural history and prognosis of cystinosis patients. However, due to its significant side effects and a strict 6-hourly dosing regimen, non-adherence to the immediate release of cysteamine bitartrate formulation (Cystagon®) is a major issue that might affect long-term outcome. Recently, a new twice-daily administered delayed-release enteric-coated formula of cysteamine bitartrate (Procysbi(TM)) has been approved by the European Medical Agency for the treatment of cystinosis, and has been shown to be safe and effective. This delayed-release cysteamine has the potential to improve compliance and hence prognosis, through its better dosing regimen, positive impact on quality of life and possibly less side-effects, and is now tested in an ongoing long-term clinical trial. Longer survival of patients with cystinosis makes transition from pediatric to adult-oriented care another challenge in cystinosis management and requires an extended multidisciplinary approach.

Evaluation of carbohydrate-cysteamine thiazolidines as pro-drugs for the treatment of cystinosis

“…Procysbi TM is proved to have a safe profile and better pharmacokinetic properties. In addition, its twice daily administration compared to Cystagon (4 times per day), might enhance patients' compliance [1,19]. Halitosis, one of the significant obstacles to patients' compliance is mainly caused by cysteamine metabolites, dimethylsulfide and methanethiol [17].…”

“…Halitosis and disagreeable sweat odor are considered to be caused by cysteamine metabolites, methanethiol and to a larger extent dimethylsulfide [17,18]. These side effects and the frequency of administration can negatively influence the compliance of patients with cysteamine [19]. Therefore, there is a great demand for new cysteamine preparations that can reduce the side effects and increase patients' compliance.…”

Effects of Coated Cysteamine on Oxidative Stress and Inflammation in Weaned Pigs

“…Cys is easily degraded and rapidly oxidized in air, or generates disulfide cystamine in solution [ 17 ]. Therefore, enteric coating of cysteamine is an effective method to prevent it from dissolving in the acidic environment of the stomach [ 18 ]. Coated cysteamine is a feed stable cysteamine hydrochloride produced by advanced microencapsulation technology, adopting an advanced microcapsule coating technology and special coating wall materials with an encapsulation rate of 100%.…”

Augmenting autophagy for prognosis based intervention of COPD-pathophysiology

“…In fact, these drugs showed an excellent control of tobacco smoke or eCV/nicotine exposure induced aggresome-pathology [10–12, 18] thus allowing a wider prospective therapeutic window that we aim to utilize to control COPD-emphysema disease progression. One of the leading candidate for autophagy inducing drug is cysteamine, based on its well-characterized properties as a potent anti-oxidant, bactericidal and mucolytic, which is currently under clinical evaluation (procysbi, cystagon or lynovex) for the treatment of other chronic diseases such as CF [77–79]. In addition, the CFTR-rescuing property of cysteamine [78, 80] will provide additional therapeutic advantage in COPD by controlling CS-induced acquired CFTR-dysfunction [12, 45].…”