scholarly journals Nucleic Acid–Based Therapeutics in Orphan Neurological Disorders: Recent Developments

2021 ◽  
Vol 8 ◽  
Author(s):  
Olga Khorkova ◽  
Jane Hsiao ◽  
Claes Wahlestedt
Keyword(s):  
Nucleic Acid ◽  
Neurological Disorders ◽  
Rational Design ◽  
Neurological Diseases ◽  
Clinical Stage ◽  
Genetic Research ◽  
Orphan Disease ◽  
Common Disease ◽  
Orphan Diseases ◽  
Recent Developments

The possibility of rational design and the resulting faster and more cost-efficient development cycles of nucleic acid–based therapeutics (NBTs), such as antisense oligonucleotides, siRNAs, and gene therapy vectors, have fueled increased activity in developing therapies for orphan diseases. Despite the difficulty of delivering NBTs beyond the blood–brain barrier, neurological diseases are significantly represented among the first targets for NBTs. As orphan disease NBTs are now entering the clinical stage, substantial efforts are required to develop the scientific background and infrastructure for NBT design and mechanistic studies, genetic testing, understanding natural history of orphan disorders, data sharing, NBT manufacturing, and regulatory support. The outcomes of these efforts will also benefit patients with “common” diseases by improving diagnostics, developing the widely applicable NBT technology platforms, and promoting deeper understanding of biological mechanisms that underlie disease pathogenesis. Furthermore, with successes in genetic research, a growing proportion of “common” disease cases can now be attributed to mutations in particular genes, essentially extending the orphan disease field. Together, the developments occurring in orphan diseases are building the foundation for the future of personalized medicine. In this review, we will focus on recent achievements in developing therapies for orphan neurological disorders.

scholarly journals Aptamer Applications in Neuroscience

2021 ◽  
Author(s):  
Meric Ozturk ◽  
Marit Nilsen-Hamilton ◽  
Muslum Ilgu
Keyword(s):  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Nucleic Acid ◽  
Brain Tumors ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Health Community ◽  
Theranostic Applications ◽  
Lateral Sclerosis

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer's disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion dis-ease, or brain tumors. Diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theranostic applications to meet these needs. This review covers pioneer studies to apply aptamers, which show promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

scholarly journals Aptamer Applications in Neuroscience

2021 ◽  
Vol 14 (12) ◽  
pp. 1260
Author(s):  
Meric Ozturk ◽  
Marit Nilsen-Hamilton ◽  
Muslum Ilgu
Keyword(s):  
Multiple Sclerosis ◽  
Amyotrophic Lateral Sclerosis ◽  
Nucleic Acid ◽  
Brain Tumors ◽  
Global Health ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Treatment Options ◽  
Health Community ◽  
Lateral Sclerosis

Being the predominant cause of disability, neurological diseases have received much attention from the global health community. Over a billion people suffer from one of the following neurological disorders: dementia, epilepsy, stroke, migraine, meningitis, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, prion disease, or brain tumors. The diagnosis and treatment options are limited for many of these diseases. Aptamers, being small and non-immunogenic nucleic acid molecules that are easy to chemically modify, offer potential diagnostic and theragnostic applications to meet these needs. This review covers pioneering studies in applying aptamers, which shows promise for future diagnostics and treatments of neurological disorders that pose increasingly dire worldwide health challenges.

scholarly journals Circulating Metabolites as Potential Biomarkers for Neurological Disorders—Metabolites in Neurological Disorders

Metabolites ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 389
Author(s):  
Amanda Donatti ◽  
Amanda M. Canto ◽  
Alexandre B. Godoi ◽  
Douglas C. da Rosa ◽  
Iscia Lopes-Cendes
Keyword(s):  
Neurological Disorders ◽  
High Performance ◽  
Current Knowledge ◽  
Neurological Diseases ◽  
Liquid Chromatography Mass Spectrometry ◽  
Relevant Research ◽  
Tissue Samples ◽  
Recent Developments ◽  
Research Findings ◽  
Potential Biomarkers

There are, still, limitations to predicting the occurrence and prognosis of neurological disorders. Biomarkers are molecules that can change in different conditions, a feature that makes them potential tools to improve the diagnosis of disease, establish a prognosis, and monitor treatments. Metabolites can be used as biomarkers, and are small molecules derived from the metabolic process found in different biological media, such as tissue samples, cells, or biofluids. They can be identified using various strategies, targeted or untargeted experiments, and by different techniques, such as high-performance liquid chromatography, mass spectrometry, or nuclear magnetic resonance. In this review, we aim to discuss the current knowledge about metabolites as biomarkers for neurological disorders. We will present recent developments that show the need and the feasibility of identifying such biomarkers in different neurological disorders, as well as discuss relevant research findings in the field of metabolomics that are helping to unravel the mechanisms underlying neurological disorders. Although several relevant results have been reported in metabolomic studies in patients with neurological diseases, there is still a long way to go for the clinical use of metabolites as potential biomarkers in these disorders, and more research in the field is needed.

Molecular insights on the dynamic stability of peptide nucleic acid functionalized carbon and boron nitride nanotubes

2021 ◽  
Vol 23 (1) ◽  
pp. 219-228
Author(s):  
Nabanita Saikia ◽  
Mohamed Taha ◽  
Ravindra Pandey
Keyword(s):  
Nucleic Acid ◽  
Boron Nitride ◽  
Nucleic Acids ◽  
Dynamic Stability ◽  
Peptide Nucleic Acid ◽  
Rational Design ◽  
Peptide Nucleic Acids ◽  
Boron Nitride Nanotubes ◽  
Molecular Hybrids ◽  
Single Wall Nanotubes

The rational design of self-assembled nanobio-molecular hybrids of peptide nucleic acids with single-wall nanotubes rely on understanding how biomolecules recognize and mediate intermolecular interactions with the nanomaterial's surface.

Microbiota-Immune System Interactions in Human Neurological Disorders

2020 ◽  
Vol 19 (7) ◽  
pp. 509-526
Author(s):  
Qin Huang ◽  
Fang Yu ◽  
Di Liao ◽  
Jian Xia
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Neurological Disorders ◽  
Brain Function ◽  
Neurological Diseases ◽  
Host Immune System ◽  
Gut Dysbiosis ◽  
Characteristic Features ◽  
Novel Therapeutic Strategies

: Recent studies implicate microbiota-brain communication as an essential factor for physiology and pathophysiology in brain function and neurodevelopment. One of the pivotal mechanisms about gut to brain communication is through the regulation and interaction of gut microbiota on the host immune system. In this review, we will discuss the role of microbiota-immune systeminteractions in human neurological disorders. The characteristic features in the development of neurological diseases include gut dysbiosis, the disturbed intestinal/Blood-Brain Barrier (BBB) permeability, the activated inflammatory response, and the changed microbial metabolites. Neurological disorders contribute to gut dysbiosis and some relevant metabolites in a top-down way. In turn, the activated immune system induced by the change of gut microbiota may deteriorate the development of neurological diseases through the disturbed gut/BBB barrier in a down-top way. Understanding the characterization and identification of microbiome-immune- brain signaling pathways will help us to yield novel therapeutic strategies by targeting the gut microbiome in neurological disease.

scholarly journals The Use, Standardization, and Interpretation of Brain Imaging Data in Clinical Trials of Neurodegenerative Disorders

2021 ◽  
Author(s):  
Adam J. Schwarz
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Neurological Disorders ◽  
Amyloid Β ◽  
Development Program ◽  
Imaging Biomarkers ◽  
Common Disease ◽  
Structural Imaging ◽  
Target Engagement ◽  
Pharmacodynamic Effect

AbstractImaging biomarkers play a wide-ranging role in clinical trials for neurological disorders. This includes selecting the appropriate trial participants, establishing target engagement and mechanism-related pharmacodynamic effect, monitoring safety, and providing evidence of disease modification. In the early stages of clinical drug development, evidence of target engagement and/or downstream pharmacodynamic effect—especially with a clear relationship to dose—can provide confidence that the therapeutic candidate should be advanced to larger and more expensive trials, and can inform the selection of the dose(s) to be further tested, i.e., to “de-risk” the drug development program. In these later-phase trials, evidence that the therapeutic candidate is altering disease-related biomarkers can provide important evidence that the clinical benefit of the compound (if observed) is grounded in meaningful biological changes. The interpretation of disease-related imaging markers, and comparability across different trials and imaging tools, is greatly improved when standardized outcome measures are defined. This standardization should not impinge on scientific advances in the imaging tools per se but provides a common language in which the results generated by these tools are expressed. PET markers of pathological protein aggregates and structural imaging of brain atrophy are common disease-related elements across many neurological disorders. However, PET tracers for pathologies beyond amyloid β and tau are needed, and the interpretability of structural imaging can be enhanced by some simple considerations to guard against the possible confound of pseudo-atrophy. Learnings from much-studied conditions such as Alzheimer’s disease and multiple sclerosis will be beneficial as the field embraces rarer diseases.

Trend of Hospital Admission and Outcome Study of Patients Admitted in a Neurology Unit at a Tertiary Care Neuroscience Hospital in Bangladesh

2018 ◽  
Vol 4 (2) ◽  
pp. 69-74
Author(s):  
Md Tauhidul Islam Chowdhury ◽  
Mohammad Shah Jahirul Hoque Choudhury ◽  
KM Ahasan Ahmed ◽  
Mohammad Sadekur Rahman Sarkar ◽  
Md Abdullah Yusuf ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Neurological Diseases ◽  
Tertiary Care ◽  
Length Of Hospital Stay ◽  
Retrospective Chart Review ◽  
Total Death ◽  
Neurological Patients ◽  
Study Population ◽  
The Mean ◽  
Day By Day

Background: Neurological disorders is becoming a growing concern both for developed and developing countries. Magnitude of the problem is increasing day by day. Among all neurological disorders, stroke is the leading cause of morbidity and mortality globally.Objectives: The purpose of the study was to see the trend of admission of patients with neurological diseases and to study the outcome of patients at referral neurology hospital in Bangladesh.Methodology: This retrospective chart review was conducted in the blue unit of the Department of Neurology at National Institute of Neurosciences and Hospital, Dhaka, Bangladesh from 1st January to 31st December 2016 for a period of one (01) year. All the admitted patients with both sexes were selected as study population. The outcome was observed among the study population.Result: A total number of 1044 patients were admitted during the study period. Majority of the patients were in the age group of the 41 to 50 years which was 417(39.9%) cases. Both male and female were in highest number in the month of May which was 63 and 48 cases respectively. The total death of the study population was 146(14.0%) cases. The mean length of hospital stay was 8.4±2.31 days.Conclusion: Middle aged male is the main bulk of the neurological patients, admitted in a referral neurology hospital in Bangladesh. Highest admission and mortality was observed in stroke patients.Journal of National Institute of Neurosciences Bangladesh, 2018;4(2): 69-74

scholarly journals Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

2020 ◽  
Vol 21 (10) ◽  
pp. 3483 ◽  
Author(s):  
Przemysław Koźmiński ◽  
Paweł Krzysztof Halik ◽  
Raphael Chesori ◽  
Ewa Gniazdowska
Keyword(s):  
Folic Acid ◽  
Combination Therapy ◽  
Autoimmune Diseases ◽  
Myasthenia Gravis ◽  
Neurological Disorders ◽  
Chemotherapeutic Agent ◽  
Neurological Diseases ◽  
Immunosuppressive Drug ◽  
Structural Analogue ◽  
Potential Benefits

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer’s disease or myasthenia gravis will be discussed.

scholarly journals Visible Light Photochemical Reactions for Nucleic Acid-Based Technologies

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 556
Author(s):  
Bonwoo Koo ◽  
Haneul Yoo ◽  
Ho Jeong Choi ◽  
Min Kim ◽  
Cheoljae Kim ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Visible Light ◽  
Chemical Reactions ◽  
Chemical Biology ◽  
Photochemical Reactions ◽  
Reaction Conditions ◽  
Promising Tool ◽  
Recent Developments ◽  
Visible Light Driven

The expanding scope of chemical reactions applied to nucleic acids has diversified the design of nucleic acid-based technologies that are essential to medicinal chemistry and chemical biology. Among chemical reactions, visible light photochemical reaction is considered a promising tool that can be used for the manipulations of nucleic acids owing to its advantages, such as mild reaction conditions and ease of the reaction process. Of late, inspired by the development of visible light-absorbing molecules and photocatalysts, visible light-driven photochemical reactions have been used to conduct various molecular manipulations, such as the cleavage or ligation of nucleic acids and other molecules as well as the synthesis of functional molecules. In this review, we describe the recent developments (from 2010) in visible light photochemical reactions involving nucleic acids and their applications in the design of nucleic acid-based technologies including DNA photocleaving, DNA photoligation, nucleic acid sensors, the release of functional molecules, and DNA-encoded libraries.

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