scholarly journals Challenges of Combination Therapies in Alzheimer’s Disease

2020 ◽  
Author(s):  
Md. Sahab Uddin
Keyword(s):  
Single Molecule ◽  
Molecular Targets ◽  
Symptomatic Treatment ◽  
Therapeutic Agents ◽  
Combination Therapies ◽  
Neuroprotective Effects ◽  
Randomized Controlled ◽  
Long Duration ◽  
Potential Benefits ◽  
End Stage

Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Until now, available therapeutic agents for AD treatment only provide symptomatic treatment. Since AD pathogenesis is multifactorial, use of a multimodal therapeutic intervention addressing several molecular targets of AD-related pathological processes seems to be the most practical approach to modify the course of AD progression. It has been demonstrated through numerous studies, that the clinical efficacy of combination therapy (CT) is higher than that of monotherapy. It is indeed difficult to combine several pharmacophores into a single molecule.  It is essential to carry out long-duration randomized controlled trials to establish whether CT delays disease progression in early AD stages. Other factors also need to be assessed in CT, such as its potential neuroprotective effects, cost-effectiveness, and a more exhaustive estimation of its potential benefits on the patients at the end-stage of AD.

scholarly journals Combination Drug Therapy for the Management of Alzheimer’s Disease

2020 ◽  
Vol 21 (9) ◽  
pp. 3272 ◽  
Author(s):  
Md. Tanvir Kabir ◽  
Md. Sahab Uddin ◽  
Abdullah Al Mamun ◽  
Philippe Jeandet ◽  
Lotfi Aleya ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Effective Treatment ◽  
Neurodegenerative Disorder ◽  
Research Priorities ◽  
Molecular Targets ◽  
Symptomatic Treatment ◽  
Therapeutic Agents ◽  
Combination Drug ◽  
Early Phases

Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Even though the number of AD patients is rapidly growing, there is no effective treatment for this neurodegenerative disorder. At present, implementation of effective treatment approaches for AD is vital to meet clinical needs. In AD research, priorities concern the development of disease-modifying therapeutic agents to be used in the early phases of AD and the optimization of the symptomatic treatments predominantly dedicated to the more advanced AD stages. Until now, available therapeutic agents for AD treatment only provide symptomatic treatment. Since AD pathogenesis is multifactorial, use of a multimodal therapeutic intervention addressing several molecular targets of AD-related pathological processes seems to be the most practical approach to modify the course of AD progression. It has been demonstrated through numerous studies, that the clinical efficacy of combination therapy (CT) is higher than that of monotherapy. In case of AD, CT is more effective, mostly when started early, at slowing the rate of cognitive impairment. In this review, we have covered the major studies regarding CT to combat AD pathogenesis. Moreover, we have also highlighted the safety, tolerability, and efficacy of CT in the treatment of AD.

Combination Therapies Using Metformin and/or Valproic Acid in Prostate Cancer: Possible Mechanistic Interactions

2019 ◽  
Vol 19 (5) ◽  
pp. 368-381 ◽  
Author(s):  
Linh N.K. Tran ◽  
Ganessan Kichenadasse ◽  
Pamela J. Sykes
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Androgen Receptor ◽  
Gene Fusion ◽  
Combination Therapies ◽  
Slowing Down ◽  
Castration Resistant ◽  
Local Pca ◽  
End Stage ◽  
Fusion Products

Prostate cancer (PCa) is the most frequent cancer in men. The evolution from local PCa to castration-resistant PCa, an end-stage of disease, is often associated with changes in genes such as p53, androgen receptor, PTEN, and ETS gene fusion products. Evidence is accumulating that repurposing of metformin (MET) and valproic acid (VPA) either when used alone, or in combination, with another therapy, could potentially play a role in slowing down PCa progression. This review provides an overview of the application of MET and VPA, both alone and in combination with other drugs for PCa treatment, correlates the responses to these drugs with common molecular changes in PCa, and then describes the potential for combined MET and VPA as a systemic therapy for prostate cancer, based on potential interacting mechanisms.

scholarly journals Advances in Membranous Nephropathy

2021 ◽  
Vol 10 (4) ◽  
pp. 607
Author(s):  
Pierre Ronco ◽  
Emmanuelle Plaisier ◽  
Hanna Debiec
Keyword(s):  
Membranous Nephropathy ◽  
Calcineurin Inhibitor ◽  
Sequential Therapy ◽  
Randomized Controlled ◽  
Therapeutic Algorithms ◽  
Long Time ◽  
Substantial Progress ◽  
Thrombotic Complications ◽  
Mixed Classes ◽  
End Stage

Membranous nephropathy (MN) is a rare auto-immune disease where the glomerulus is targeted by circulating auto-antibodies mostly against podocyte antigens, which results in the formation of electron-dense immune complexes, activation of complement and massive proteinuria. MN is the most common cause of nephrotic syndrome in adults leading to severe thrombotic complications and kidney failure. This review is focused on the recent therapeutic and pathophysiological advances that occurred in the last two years. For a long time, we were lacking a head-to-head comparison between cyclophosphamide considered as the gold standard therapy and other medications, notably rituximab. Substantial progress has been achieved owing to three randomized controlled trials. MENTOR (Membranous Nephropathy Trial of Rituximab) and STARMEN (Sequential Therapy with Tacrolimus and Rituximab in Primary Membranous Nephropathy) conclusively established that calcineurin inhibitor-based regimens are slower to result in an immunologic response than rituximab or cyclophosphamide, achieve fewer complete clinical remissions, and are less likely to maintainremission. Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO) suggested that competition between cyclophosphamide and rituximab remains open. Given the technological leap combining laser microdissection of glomeruli and mass spectrometry of solubilized digested proteins, four “new antigens” were discovered including NELL-1 and Semaphorin 3B in so-called primary MN, and exostosins 1 and 2 and NCAM 1 in lupus MN. NELL-1 is associated with about 8% of primary MN and is characterized by segmental immune deposits and frequent association with cancer (30%). Semaphorin 3B-associated MN usually occurs in children, often below the age of two years, where it is the main antigen, representing about 16% of non-lupus MN in childhood. Exostosins 1/2 and NCAM 1 are associated with 30% and 6% of lupus MN, respectively. Exostosins 1/2 (EXT1/2) staining is associated with a low rate of end-stage kidney disease (ESKD) even in mixed classes III/IV+V. These findings already lead to revisiting the diagnostic and therapeutic algorithms toward more personalized medicine.

scholarly journals Antidiabetic Effects of Resveratrol: The Way Forward in Its Clinical Utility

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Omolola R. Oyenihi ◽  
Ayodeji B. Oyenihi ◽  
Anne A. Adeyanju ◽  
Oluwafemi O. Oguntibeju
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Utility ◽  
Therapeutic Agent ◽  
Molecular Targets ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Antidiabetic Drug ◽  
Near Future ◽  
Antidiabetic Effects ◽  
The Way

Despite recent advances in the understanding and management ofdiabetes mellitus, the prevalence of the disease is increasing unabatedly with resulting disabling and life-reducing consequences to the global human population. The limitations and side effects associated with current antidiabetic therapies have necessitated the search for novel therapeutic agents. Due to the multipathogenicity ofdiabetes mellitus,plant-derived compounds with proven multiple pharmacological actions have been postulated to “hold the key” in the search for an affordable, efficacious, and safer therapeutic agent in the treatment of the disease and associated complications. Resveratrol, a phytoalexin present in few plant species, has demonstrated beneficial antidiabetic effects in animals and humans through diverse mechanisms and multiple molecular targets. However, despite the enthusiasm and widespread successes achieved with the use of resveratrol in animal models ofdiabetes mellitus, there are extremely limited clinical data to confirm the antidiabetic qualities of resveratrol. This review presents an update on the mechanisms of action and protection of resveratrol indiabetes mellitus, highlights challenges in its clinical utility, and suggests the way forward in translating the promising preclinical data to a possible antidiabetic drug in the near future.

Sign in / Sign up

Export Citation Format

Share Document