BACKGROUND: Melasma is a chronic pigmentary disorder. In this study, an innovative cream combining cysteamine and tranexamic acid (TXA) was assessed.
OBJECTIVE: To evaluate the safety, efficacy, and patient satisfaction of a novel nano-formulated cysteamine and TXA combination cream in treating subjects with epidermal melasma.
METHODS:   Fifty (50) randomized subjects participated and received cysteamine and TXA combination cream. The cream was applied for 30 minutes daily for a 3-month duration. Treatment effectiveness, safety, patient satisfaction, and adherence were evaluated.
RESULTS: A continuous improvement in melasma was observed, with modified Melasma Area and Severity Index (mMASI) scores improving by 40%, 57%, and 63% at 30, 60, and 90 days, respectively. The primary endpoint of a decrease in mMASI scores was met, with 91% of participants experiencing melasma improvement. Patient Satisfaction and Patient Adherence scores indicated satisfaction. Convenience exhibited the strongest correlation with patient adherence.  Conclusion: Nano-formulated cysteamine and TXA combination cream showed significant efficacy in decreasing mMASI score while demonstrating a strong safety profile and patient satisfaction.  J Drugs Dermatol. 2024;23(7):529-537.     doi:10.36849/JDD.7765R1.

Metal nanoclusters (NCs) as a new kind of luminophore have acquired sufficient interest, but their widespread application is restricted on account of their relatively low electrochemiluminescence (ECL) efficiency. Then, aqueous metal NCs with high ECL efficiency were strongly anticipated, especially for the ultrasensitive analysis of biomarkers. Herein, a near-infrared (NIR) ECL biosensing strategy for the test of neuron-specific enolase (NSE) was proposed by utilizing N-acetyl-l-cysteine (NAC)- and cysteamine (Cys)-stabilized gold NCs (NAC/Cys-AuNCs) as ECL emitters with the NIR ECL emission around 860 nm and a metal-organic framework/palladium nanocubes (ZIF-67/PdNCs) hybrid as the coreaction accelerator through their admirable electrocatalytic activity. The NIR emission would reduce photochemical injury to the samples and even realize nondestructive analysis with highly strong susceptibility and suitability. Furthermore, the utilization of ZIF-67/PdNCs could improve the ECL response of NAC/Cys-AuNCs by facilitating the oxidation of the coreactant triethylamine (TEA), leading to the production of a larger quantity of reducing intermediate radical TEA•+. Consequently, NAC/Cys-AuNCs with ZIF-67/PdNCs displayed 2.7 fold enhanced ECL emission compared with the single NAC/Cys-AuNCs using TEA as the coreactant. In addition, HWRGWVC (HWR), a heptapeptide, was introduced to immobilize antibodies for the specially binding Fc fragment of the antibodies, which improved the binding efficiency and sensitivity. As a result, a \"signal-on\" immunosensor for NSE analysis was obtained with an extensive linear range of 0.1 to 5 ng/mL and a low limit of detection (0.033 fg/mL) (S/N = 3). This study provides a wonderful method for the development of an efficient nondestructive immunoassay.

Glioblastoma (GBM) cells are highly invasive, infiltrating the surrounding normal brain tissue, thereby limiting the efficacy of surgical resection and focal radiotherapy. Cysteamine, a small aminothiol molecule that is orally bioavailable and approved for cystinosis, has potential as a cancer treatment by inhibiting tumor cell invasion and metastasis. Here we demonstrate that these potential therapeutic effects of cysteamine are likely due to the inhibition of matrix metalloproteinases (MMPs) in GBM. In vitro assays confirmed that micromolar concentrations of cysteamine were not cytotoxic, enabling the interrogation of the cellular effects without confounding tumor cell loss. Cysteamine\'s inhibition of MMP activity, especially the targeting of MMP2, MMP9, and MMP14, was observed at micromolar concentrations, suggesting the mechanism of action in suppressing invasion and cell migration is by inhibition of these MMPs. These findings suggest that achievable micromolar concentrations of cysteamine effectively inhibit cancer cell invasion and migration in GBM, supporting the potential for use as an adjunct cancer treatment.

Cystinosis is a lysosomal storage disorder usually presenting with renal disease in infancy. As soon as the diagnosis is made, cysteamine (a cystine-depleting medication), is started, significantly improving life expectancy. We describe a young woman taking lifelong cysteamine for nephropathic cystinosis, who became acutely encephalopathic with a spastic tetraparesis secondary to cysteamine toxicity, which was potentially worsened by copper deficiency. On replacing copper and reducing the dose of cysteamine, she made a full neurological recovery. We discuss the case, and review cystinosis and what is known about cysteamine toxicity.

Cystinosis is a rare lysosomal storage disorder caused by autosomal recessive mutations in the CTNS gene that encodes for the cystine transporter cystinosin, which is expressed on the lysosomal membrane mediating the efflux of cystine. Cysteamine bitartrate is a cystine-depleting aminothiol agent approved for the treatment of cystinosis in children and adults. In this study, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of cysteamine levels in plasma samples. This LC-MS/MS method was validated according to the European Medicines Agency (EMA)\'s guidelines for bioanalytical method validation. An ultra-performance liquid chromatograph (UPLC) coupled with a 6470 mass spectrometry system was used for cysteamine determination. Our validated method was applied to plasma samples from n = 8 cystinosis patients (median, interquartile range (IQR) = 20.5, 8.5-26.0 years). The samples were collected before cysteamine oral administration (pre-dose) and 1 h after (post-dose). Our bioanalytical method fulfilled the regulatory guidelines for method validation. The cysteamine plasma levels in pre-dose samples were 2.57 and 1.50-3.31 μM (median and IQR, respectively), whereas the post-dose samples reported a cysteamine median concentration of 28.00 μM (IQR: 17.60-36.61). Our method allows the rapid determination of cysteamine plasma levels. This method was successfully used in cystinosis patients and, therefore, could be a useful tool for the evaluation of therapy adherence and for future pharmacokinetic (PK) studies involving a higher number of subjects.

Present work reports, the development of a novel electrochemical sensor based on a diazonium-coupling reaction and covalent attachment of the -NH2 group of cysteamine (Cyst) on screen-printed carbon electrode (SPCE), for simultaneous determination of Pb(II) and Cd(II). Initially, the in-situ generated 4-carboxyphenyl (4-CP) diazonium salt was electro-grafted to generate 4-CP/SPCE, followed by covalent bonding of terminal carboxylic group of 4-CP with -NH2 group of Cyst to give Cyst/4-CP/SPCE. The modified electrode showed an enhanced selectivity and sensitivity toward the quantification of Pb(II) and Cd(II) using square wave anodic stripping voltammetry (SWASV) without mutual interference. Under optimal experimental conditions, the newly designed sensor showed a wide linear range of 0.01 µM to 0.7 µM. The limit of detection (LOD) obtained was 0.882 nM (0.09 ppb) and 0.65 nM (0.134 ppb) for Cd(II) and Pb(II), respectively. The modified SPCE exhibited good stability, selectivity, and reproducibility. Furthermore, the sensor was successfully applied for the determination of Pb(II) and Cd(II) ions in water samples which illustrated excellent recoveries in different spiked samples and the results were in line with the standard ICP-AES analysis.

Glutathione (GSH) is a major endogenous antioxidant, and its depletion has been observed in several brain diseases including epilepsy. Previous studies in our laboratory have shown that dimercaprol (DMP) can elevate GSH via post-translational activation of glutamate cysteine ligase (GCL), the rate limiting GSH biosynthetic enzyme and inhibit neuroinflammation in vitro. Here we determined 1) the role of cysteamine as a new mechanism by which DMP increases GSH biosynthesis and 2) its ability to inhibit neuroinflammation and neuronal injury in the rat kainate model of epilepsy. DMP depleted cysteamine in a time- and concentration-dependent manner in a cell free system. To guide the in vivo administration of DMP, its pharmacokinetic profile was determined in the plasma, liver, and brain. The results confirmed DMP\'s ability to cross the blood-brain-barrier. Treatment of rats with DMP (30 mg/kg) depleted cysteamine in the liver and hippocampus that was associated with increased GCL activity in these tissues. GSH levels were significantly increased (20 %) in the hippocampus 1 h after 30 mg/kg DMP administration. Following DMP (30 mg/kg) administration once daily, a marked attenuation of GSH depletion was seen in the SE model. SE-induced inflammatory markers including cytokine release, microglial activation, and neuronal death were significantly attenuated in the hippocampus with DMP treatment. Taken together, these results highlight the importance of restoring redox status with rescue of GSH depletion by DMP in post epileptogenic insults.

Gold nanorods (AuNRs) have attracted significant attention over the past several decades for a variety of applications and there has been steady progress with regards to their synthesis and modification. Despite these advances, the assembly of AuNRs into well-organized hierarchical assemblies remains a formidable challenge. Specifically, there is a need for tools that can fabricate assemblies of nanorods over large length scales at low cost with the potential for high-throughput manufacturing. Langmuir-Blodgettry is a monolayer deposition technique which has been primarily applied to amphiphilic molecules, but which has recently shown promise for the ordering of functionalized nanoparticles residing at the air-water interface. In this work, Langmuir-Blodgett deposition is explored for the formation of AuNR arrays for enhanced surface-enhanced Raman spectroscopy (SERS) sensing. In particular, both surface modification of the AuNRs as well as subphase modification with cysteamine were evaluated for AuNR array fabrication.

UNASSIGNED: Postinflammatory hyperpigmentation (PIH) is a common sequela of acne vulgaris. Topical treatment with hydroquinone is the standard treatment, but may be associated with complications. Cysteamine is a relatively safe depigmenting agent with an observed depigmenting effect. We designed this study to assess the efficacy of a cysteamine 5% cream in treating acne-induced PIH.
UNASSIGNED: Twenty-eight out of 32 participants finalized this investigator-blind, randomized, and controlled trial (registered in Iranian Registry of Clinical Trials [IRCTID: IRCT20140212016557N5]). We randomized the patients to apply either cysteamine 5% or hydroquinone 4%/ascorbic acid 3% (HC) cream. Postacne hyperpigmentation index (PAHPI) and melanin index were the assessment measures after four months of treatment. We evaluated the quality of life by the Dermatology Life Quality Index (DLQI) questionnaire.
UNASSIGNED: Both cysteamine and HC cream significantly decreased the PAHPI score and melanin index of acne-induced PIH patients (p<0.05). The decrease in PAHPI score and melanin index were not significantly different in treatment groups after four months (p>0.05). Quality of life ameliorated significantly only with cysteamine treatment. However, no significant change in quality of life was observed between groups.
UNASSIGNED: Limitations of our study include the relatively small sample size and absence of follow-up.
UNASSIGNED: Cysteamine cream is an effective treatment of post-acne PIH, with similar efficacy to the accepted treatment of PIH, i.e., hydroquinone cream.

Cystinosis is a rare, autosomal recessive, lysosomal storage disease caused by mutations in the gene CTNS, leading to cystine accumulation in the lysosomes. While cysteamine lowers the cystine levels, it does not cure the disease, suggesting that CTNS exerts additional functions besides cystine transport. This study investigated the impact of infantile and juvenile CTNS mutations with discrepant genotype/phenotype correlations on CTNS expression, and subcellular localisation and function in clinically relevant cystinosis cell models to better understand the link between genotype and CTNS function. Using CTNS-depleted proximal tubule epithelial cells and patient-derived fibroblasts, we expressed a selection of CTNSmutants under various promoters. EF1a-driven expression led to substantial overexpression, resulting in CTNS protein levels that localised to the lysosomal compartment. All CTNSmutants tested also reversed cystine accumulation, indicating that CTNSmutants still exert transport activity, possibly due to the overexpression conditions. Surprisingly, even CTNSmutants expression driven by the less potent CTNS and EFS promoters reversed the cystine accumulation, contrary to the CTNSG339R missense mutant. Taken together, our findings shed new light on CTNS mutations, highlighting the need for robust assessment methodologies in clinically relevant cellular models and thus paving the way for better stratification of cystinosis patients, and advocating for the development of more personalized therapy.