Current Pharmaceutical Design - Volume 28, Issue 11, 2022

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired immune-mediated polyradiculoneuropathy leading to disability via inflammatory demyelination of peripheral nerves. Various therapeutic approaches with different mechanisms of action are established for the treatment of CIDP. Of those, corticosteroids, intravenous or subcutaneous immunoglobulin, or plasma exchange are established first-line therapies as suggested by the recently revised EAN/PNS guidelines for the management of CIDP. In special cases, immunosuppressants or rituximab may be used. Novel therapeutic approaches currently undergoing clinical studies include molecules or monoclonal antibodies interacting with Fc receptors on immune cells to alleviate immune-mediated neuronal damage. Despite various established therapies and the current development of novel therapeutics, treatment of CIDP remains challenging due to an heterogeneous disease course and the lack of surrogate parameters to predict the risk of clinical deterioration. This review summarizes established therapies for CIDP and provides an outlook on future therapeutic approaches.

Inflammatory myopathies, in short, myositis, are heterogeneous disorders that are characterized by inflammation of skeletal muscle and weakness of arms and legs. Research over the past few years has led to a new understanding regarding the pathogenesis of myositis. The new insights include different pathways of the innate and adaptive immune response during the pathogenesis of myositis. The importance of non-inflammatory mechanisms such as cell stress and impaired autophagy has been recently described. New target-specific drugs for myositis have been developed and are currently being tested in clinical trials. In this review, we discuss the mechanisms of action of pharmacological standards in myositis and provide an outlook of future treatment approaches.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease, which affects a wide range of organs with variable clinical features. Involvement of the nervous system is a challenging and multifaceted manifestation of the disease, presenting with a broad range of symptoms. Neuropsychiatric lupus (NPSLE) encompasses seven syndromes of the peripheral and 12 of the central nervous system, associated with a high disease burden. Despite advances in the management of SLE, NP manifestations still pose a challenge to clinicians. First, diagnosis and attribution of SLE are difficult due to the lack of specific biomarkers or imaging modalities. Second, therapeutic options are limited, and evidence is mainly based on case reports and expert consensus, as clinical trials are sparse. Moreover, no validated outcome measure on disease activity exists. Current recommendations for treatment include supportive as well as immunosuppressive medication, depending on the type and severity of manifestations. As NPSLE manifestations are increasingly recognized, a broader spectrum of therapeutic options can be expected.

Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disease leading to progressive and, in many cases, severe muscle weakness and atrophy in the natural disease course. An increasing number of gene-based treatment options have become available in recent years. Growing knowledge regarding the underlying genetic mechanisms makes the disease well amenable to them. Over the past few years, data on new treatments, their mechanisms of action and therapeutic outcomes have been published, reflecting the current dynamics in this field. With the approval of the antisense oligonucleotide nusinersen, the vector-based therapy with onasemnogene abeparvovec and the small molecule splicing modifier risdiplam, three gene therapeutic drugs are available for the treatment of SMA showing improvement in motor function. But in the pivotal studies, several relevant parameters have not been addressed. There is a data gap for the treatment outcome of adult individuals with SMA as well as for several other relevant outcome parameters, like bulbary or ventilatory function. With increasing treatment options, additional individual therapies have become necessary. Studies on combination therapies or switch of therapy, e.g., the sequential administration of onasemnogen abeparvovec and nusinersen, are necessary. An overview of current developments in the field of therapeutic options for adult SMA is presented. Important characteristics of each therapeutic options are discussed so that the reader can comprehend underlying pathophysiological mechanisms as well as advantages and disadvantages of each therapy. The focus is on gene-based treatment options, but options beyond this are also addressed.

Osteoporosis is a common localized or systemic skeletal illness in the clinic, characterized by bone production weakness and increased bone resorption, resulting in a reduction in bone mineral density (BMD), and affecting mostly postmenopausal women. The risk of osteoporosis or even osteoporotic fracture increases as age increases, putting more pressure on society and families. Although anti-osteoporosis drugs have been developed, some side effects are still observed in the treatment group. Hence the need for more reasonable therapeutic strategies. Exosomes are nanosized extracellular vesicles (EVs) secreted virtually by all types of cells in vivo, which play an important role in intercellular communication. Compared with conventional drugs and stem cells transplantation therapy, exosomes have apparent advantages of lower toxicity and immunogenicity. Exosomes contain many functional molecules, such as proteins, lipids, mRNAs, microRNAs (miRNAs), which can be transferred into recipient cells to regulate a series of signaling pathways and influence physiological and pathological behavior. In this review, we briefly summarize the current knowledge of exosomes and the therapeutic potential of exosomal miRNAs derived from mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, and macrophages in osteoporosis. Finally, a prospect of new treatment strategies for osteoporosis using new biomaterial scaffolds combined with exosomes is also given.

Background: Recent studies have been reported emerging polymeric nanoparticles as a promising particulate carrier system for controlled and targeted drug delivery. Stimuli-responsive nanocarriers have shown characteristics, such as high drug uptake at specific sites or targeted cells with an advantage of no drug leakage. These stimuli-responsive polymeric systems are used to functionalize nanocarriers, such as dendrimers, metallic nanoparticles, polymeric nanoparticles, liposomal nanoparticles, and quantum dots. Objective: The study reviews the potential of smart stimuli-responsive carriers for therapeutic application and their behavior in external or internal stimuli, like pH, temperature, redox, light, and magnetic field. These stimuli- responsive drug delivery systems exhibit different drug release patterns in in vitro and in vivo studies. Stimuli- responsive nanocarriers are useful for both hydrophilic and hydrophobic drugs and release them on applied stimulus. This review highlights the recent development in the physical properties of polymeric materials and their application in stimuli-responsive specific drug delivery. Conclusion: The stimuli (smart, intelligent, programmable) drug delivery systems provide site-specific drug delivery with potential therapy for cancer, neurodegenerative, and lifestyle disorders. The stimuli-responsive- based nanocarriers are developing at a fast pace, and there is a huge demand for biocompatible and biodegradable responsive polymers for effective and safe delivery.

Introduction: Metastasis of primary pancreatic cancer (PC) to adjacent or distant organs is responsible for the poor survival rate of affected individuals. Chemotherapy, radiotherapy, and immunotherapy are currently being prescribed to treat PC in addition to surgical resection. Surgical resection is the preferred treatment for PC that leads to 20% of 5-year survival, but only less than 20% of patients are eligible for surgical resection because of the poor prognosis. To improve the prognosis and clinical outcome, early diagnostic markers need to be identified, and targeting them would be of immense benefit to increase the efficiency of the treatment. Cell migration-inducing hyaluronan-binding protein (CEMIP) is identified as an important risk factor for the metastasis of various cancers, including PC. Emerging studies have pointed out the crucial role of CEMIP in the regulation of various signaling mechanisms, leading to enhanced migration and metastasis of PC. Methods: The published findings on PC metastasis, phytoconstituents, and CEMIP were retrieved from Pubmed, ScienceDirect, and Cochrane Library. Computational tools, such as gene expression profiling interactive analysis (GEPIA) and Kaplan-Meier (KM) plotter, were used to study the relationship between CEMIP expression and survival of PC individuals. Results: Gene expression analysis using the GEPIA database identified a stupendous increase in the CEMIP transcript in PC compared to adjacent normal tissues. KM plotter analysis revealed the impact of CEMIP on the overall survival (OS) and disease-free survival (DFS) among PC patients. Subsequently, several risk factors associated with PC development were screened, and their ability to regulate CEMIP gene expression was analyzed using computational tools. Conclusion: The current review is focused on gathering information regarding the regulatory role of phytocomponents in PC migration and exploring their possible impact on the CEMIP expression.