Immunotargeting of extracellular tau could slow the prion-like spreading of neurodegeneration. Albert et al. report that antibodies that recognize a central epitope on tau are the most effective at blocking both seeding and propagation of tau pathological species in transgenic mouse models seeded by materials derived from Alzheimer’s disease brains.
Local ocular delivery of cyclosporine A (CsA) is the preferred method for CsA delivery as a treatment for ocular inflammatory diseases such as uveitis, corneal healing, vernal keratoconjunctivitis and dry eye disease. However, due to the large molecular weight and hydrophobic nature of CsA and the natural protective mechanisms of the eye, achieving therapeutic levels of CsA in ocular tissues can be difficult. This review gives a comprehensive overview of the current products available to clinicians as well as emerging drug delivery solutions that have been developed at both the academic and industry levels.
The identification of an effective disease-modifying treatment for the neurodegenerative progression in Parkinson's disease (PD) remains a major challenge. Epidemiological studies have reported that intake of statins, cholesterol lowering drugs, could be associated to a reduced risk of developing PD. In-vivo studies suggest that statins may reduce the severity of dopaminergic neurodegeneration. The trophic potential of statins and their impact on the expression of dopaminergic synaptic markers and dopamine (DA) transport function in SH-SY5Y cells has been investigated. The findings showed that statin treatment induces neurite outgrowth involving a specific effect on the complexity of the neurite branching pattern. Statins increased the levels of presynaptic dopaminergic biomarkers such as vesicular monoamine transporter 2 (VMAT2), synaptic vesicle glycoproteins 2A and 2C (SV2C), and synaptogyrin-3 (SYNGR3). Gene expression analysis confirmed a rapid statin-induced up-regulation of VMAT2-, SV2C-, and SYNGR3-mRNA levels. Assessment of [(3) H]DA transport in statin-treated cells showed a reduction in DA uptake concomitant to a modification of VMAT2 pharmacological properties. It was also observed that a nuclear translocation of the sterol regulatory element-binding protein 1 (SREBP-1). The results suggested that statins induced phenotypic changes in dopaminergic cells characterized by an increase of growth, complexity of structural synaptic elements, and expression of key presynaptic proteins with functional impact on the DA transport capacity. Statin-induced changes are likely the result of a downstream modulation of SREBP-1 pathway. Overall, these mechanisms may contribute to the neuroprotective or neurorestorative effects observed in the dopaminergic system and strengthen the therapeutic potential of statins for PD.
The development of oral pediatric forms by pharmaceutical companies is still insufficient. In fact, many drugs used in paediatric oncology, such as temozolomide, are not labeled and adapted for paediatric use. Temozolomide (TMZ) is an alkylating agent used as the standard of care for many adult and pediatric brain tumours, such as neuroblastoma, glioblastoma and medulloblastoma. The present study was carried out to propose a suitable and palatable formulation of the oral liquid preparation of TMZ. The suspension is composed of TMZ suspended in SyrSpend SF pH 4, as well as TMZ crystallization stabilizing agents and sweetening agents. To reach this formulation, several taste-masking agents were evaluated. Here, we describe the method of preparation of the formation as well as the monocentric population treated with the formulation over a 5–year period. A 20 mg/mL TMZ suspension was developed. TMZ suspension is stable for 6 weeks, stored between 2 and 8 degrees, protected from light, and compatible with nasogastric tubes. Thirty-eight patients participated in the palatability study and choose cola flavour, and 104 patients were treated in Gustave Roussy with the developed suspension; no unexpected event was reported. To conclude, we propose here a new TMZ liquid formulation which is stable for at least 6 weeks and well-tolerated with extensive feedback.
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