scholarly journals Novel treatments and trials in COVID-19

2022 ◽  
pp. 109-120
Author(s):  
Andrew Conway Morris ◽  
Allison Tong
Keyword(s):  
Novel Treatments

Lighting a path: genetic studies pinpoint neurodevelopmental mechanisms in autism and related disorders

2012 ◽  
Vol 14 (3) ◽  
pp. 239-252
Keyword(s):  
Molecular Mechanisms ◽  
Protein Localization ◽  
Regulation Of Gene Expression ◽  
Neuronal Cell ◽  
Mrna Splicing ◽  
Genetic Mutations ◽  
Scaffolding Proteins ◽  
Molecular Processes ◽  
Genetic Studies ◽  
Novel Treatments

In this review, we outline critical molecular processes that have been implicated by discovery of genetic mutations in autism. These mechanisms need to be mapped onto the neurodevelopment step(s) gone awry that may be associated with cause in autism. Molecular mechanisms include: (i) regulation of gene expression; (ii) pre-mRNA splicing; (iii) protein localization, translation, and turnover; (iv) synaptic transmission; (v) cell signaling; (vi) the functions of cytoskeletal and scaffolding proteins; and (vii) the function of neuronal cell adhesion molecules. While the molecular mechanisms appear broad, they may converge on only one of a few steps during neurodevelopment that perturbs the structure, function, and/or plasticity of neuronal circuitry. While there are many genetic mutations involved, novel treatments may need to target only one of few developmental mechanisms.

Epigenetic modifications in acute lymphoblastic leukemia: From cellular mechanisms to therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Ezzatollah Fathi ◽  
Raheleh Farahzadi ◽  
Soheila Montazersaheb ◽  
Yasin Bagheri
Keyword(s):  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
Histone Modification ◽  
Epigenetic Modification ◽  
Lymphoblastic Leukemia ◽  
Underlying Mechanism ◽  
Methylation Pattern ◽  
Epigenetic Alterations ◽  
Cellular Mechanisms ◽  
Novel Treatments

Background:: Epigenetic modification pattern is considered as a characteristic feature in blood malignancies. Modifications in the DNA methylation modulators are recurrent in lymphoma and leukemia, so that, the distinct methylation pattern defines different types of leukemia. Generally, the role of epigenetics is less understood and most investigations are focused on genetic abnormalities and cytogenic studies to develop novel treatments for patients with hematologic disorders. Recently, understanding the underlying mechanism of acute lymphoblastic leukemia (ALL), especially epigenetic altera-tions as a driving force in the development of ALL opens a new era of investigation for developing promising strategy, be-yond available conventional therapy. Objective:: This review will focus on a better understanding of the epigenetic mechanisms in cancer development and pro-gression, with an emphasis on epigenetic alterations in ALL including, DNA methylation, histone modification, and mi-croRNA alterations. Other topics that will be discussed include the use of epigenetic alterations as a promising therapeutic target in order to develop novel well-suited approaches against ALL. Conclusion:: According to the literature review, leukemogenesis of ALL is extensively influenced by epigenetic modifica-tions, particularly DNA hyper-methylation, histone modification, and miRNA alteration.

Recent Updates in the Alzheimer’s Disease Etiopathology and Possible Treatment Approaches: A Narrative Review of Current Clinical Trials

2020 ◽  
Vol 13 (4) ◽  
pp. 273-294 ◽  
Author(s):  
Elahe Zarini-Gakiye ◽  
Javad Amini ◽  
Nima Sanadgol ◽  
Gholamhassan Vaezi ◽  
Kazem Parivar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Small Molecules ◽  
Clinical Trial Design ◽  
Treatment Approaches ◽  
Drug Candidates ◽  
Novel Treatments ◽  
Approved Drugs ◽  
Tau Aggregation

Background: Alzheimer’s disease (AD) is the most frequent subtype of incurable neurodegenerative dementias and its etiopathology is still not clearly elucidated. Objective: Outline the ongoing clinical trials (CTs) in the field of AD, in order to find novel master regulators. Methods: We strictly reviewed all scientific reports from Clinicaltrials.gov and PubMed databases from January 2010 to January 2019. The search terms were “Alzheimer's disease” or “dementia” and “medicine” or “drug” or “treatment” and “clinical trials” and “interventions”. Manuscripts that met the objective of this study were included for further evaluations. Results: Drug candidates have been categorized into two main groups including antibodies, peptides or hormones (such as Ponezumab, Interferon β-1a, Solanezumab, Filgrastim, Levemir, Apidra, and Estrogen), and naturally-derived ingredients or small molecules (such as Paracetamol, Ginkgo, Escitalopram, Simvastatin, Cilostazo, and Ritalin-SR). The majority of natural candidates acted as anti-inflammatory or/and anti-oxidant and antibodies exert their actions via increasing amyloid-beta (Aβ) clearance or decreasing Tau aggregation. Among small molecules, most of them that are present in the last phases act as specific antagonists (Suvorexant, Idalopirdine, Intepirdine, Trazodone, Carvedilol, and Risperidone) or agonists (Dextromethorphan, Resveratrol, Brexpiprazole) and frequently ameliorate cognitive dysfunctions. Conclusion: The presences of a small number of candidates in the last phase suggest that a large number of candidates have had an undesirable side effect or were unable to pass essential eligibility for future phases. Among successful treatment approaches, clearance of Aβ, recovery of cognitive deficits, and control of acute neuroinflammation are widely chosen. It is predicted that some FDA-approved drugs, such as Paracetamol, Risperidone, Escitalopram, Simvastatin, Cilostazoand, and Ritalin-SR, could also be used in off-label ways for AD. This review improves our ability to recognize novel treatments for AD and suggests approaches for the clinical trial design for this devastating disease in the near future.

scholarly journals Evaluation of the effects of acetylcholinesterase inhibitors in the zebrafish touch-evoked response: quantitative vs. qualitative assessment

2020 ◽  
Vol 32 (1) ◽  
Author(s):  
Laura Guzman ◽  
Gisela Besa ◽  
Daniela Linares ◽  
Lara González ◽  
Caterina Pont ◽  
...  
Keyword(s):  
Neurological Diseases ◽  
Acetylcholinesterase Inhibitors ◽  
Cost Effective ◽  
Evoked Response ◽  
New Drugs ◽  
Screening Tools ◽  
Qualitative Assessment ◽  
Toxicity Screening ◽  
Novel Treatments ◽  
Ache Inhibitors

Abstract Background The difficulty of finding new treatments for neurological diseases with great impact in our society like Alzheimer’s disease can be ascribed in part to the complexity of the nervous system and the lack of quick and cost-effective screening tools. Such tools could not only help to identify potential novel treatments, but could also be used to test environmental contaminants for their potential to cause neurotoxicity. It has been estimated that 5–10% of the anthropogenic chemicals are developmental neurotoxic (DNT) and exposure to DNT compounds has been linked to several neurological diseases. Within this study we were testing the applicability of a quick and cost-effective behavioural test using zebrafish embryos: the touch-evoked response assay, in this case, an assay evaluating the swimming response to a tap in the tail. Two acetylcholinesterase (AChE) inhibitors positive controls (paraoxon and huprine Y), as well as 10 huprine-derivative compounds were tested and the results were evaluated using 2 different methods, a quantitative and a qualitative one. Results We could show that the methodology presented is able to detect behavioural effects of AChE inhibitors. A good correlation between the results obtained with the quantitative and the qualitative method was obtained (R2 = 0.84). Conclusions Our proposed method enables combination of screening for new drugs with toxicity screening in a whole embryo model alternative to animal experimentation, thereby merging 2 drug development steps into one.

scholarly journals Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

2021 ◽  
Vol 14 (5) ◽  
pp. 458
Author(s):  
Barbara Miziak ◽  
Barbara Błaszczyk ◽  
Stanisław J. Czuczwar
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Ischemia ◽  
Neurodegenerative Disorder ◽  
Neuropsychiatric Symptoms ◽  
Antidepressant Drugs ◽  
Cancer Drug ◽  
Novel Treatments ◽  
Close Relationship ◽  
Approved Drugs

Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.

scholarly journals Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 30
Author(s):  
Marthinus Janse van Vuuren ◽  
Theodore Albertus Nell ◽  
Jonathan Ambrose Carr ◽  
Douglas B. Kell ◽  
Etheresia Pretorius
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Systemic Inflammation ◽  
Cell Damage ◽  
Vascular Dysfunction ◽  
Iron Chelation ◽  
Gut Health ◽  
Novel Treatments ◽  
Randomized Controlled Clinical Trials ◽  
Iron Dysregulation

Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here, we bring together evidence that the development and presence of PD depends on specific sets of interlinking factors that include neuroinflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, and gut and periodontal dysbiosis. We argue that there is significant evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the development of PD. We also discuss the processes whereby bacterial inflammagens may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that iron chelation, pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments in PD. A most important consideration, however, is that these therapeutic options need to be validated and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide variety of novel treatments, which may relieve the characteristic motor and nonmotor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease.

scholarly journals EEG Fractal Analysis Reflects Brain Impairment after Stroke

Entropy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. 592
Author(s):  
Maria Rubega ◽  
Emanuela Formaggio ◽  
Franco Molteni ◽  
Eleonora Guanziroli ◽  
Roberto Di Marco ◽  
...  
Keyword(s):  
Early Stage ◽  
Brain Activity ◽  
Phase 1 ◽  
Behavioral Changes ◽  
Stroke Survivors ◽  
Eeg Signals ◽  
Novel Treatments ◽  
Fractal Measures ◽  
Underlying Mechanisms ◽  
Random Fluctuations

Stroke is the commonest cause of disability. Novel treatments require an improved understanding of the underlying mechanisms of recovery. Fractal approaches have demonstrated that a single metric can describe the complexity of seemingly random fluctuations of physiological signals. We hypothesize that fractal algorithms applied to electroencephalographic (EEG) signals may track brain impairment after stroke. Sixteen stroke survivors were studied in the hyperacute (<48 h) and in the acute phase (∼1 week after stroke), and 35 stroke survivors during the early subacute phase (from 8 days to 32 days and after ∼2 months after stroke): We compared resting-state EEG fractal changes using fractal measures (i.e., Higuchi Index, Tortuosity) with 11 healthy controls. Both Higuchi index and Tortuosity values were significantly lower after a stroke throughout the acute and early subacute stage compared to healthy subjects, reflecting a brain activity which is significantly less complex. These indices may be promising metrics to track behavioral changes in the very early stage after stroke. Our findings might contribute to the neurorehabilitation quest in identifying reliable biomarkers for a better tailoring of rehabilitation pathways.

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