SWINGS AND ROUNDABOUTS IN CNS DRUG BIOMARKERS

Author(s):  
M.B. Isaac ◽  
S. Vamvakas

Despite substantial advances in the understanding of central nervous system (CNS) disorders, healthcare systems worldwide face an unprecedented challenge in dealing with the unmet needs in this area (1). Meanwhile, the CNS drug pipeline looks worryingly dry. There are several reasons for this, including the obvious complexity of the CNS, a lack of interdisciplinary collaborations, increased drug development costs and the higher risk of clinical failure of CNS drugs, compared with those in other areas of drug development. The year 2016 was also disappointing in terms of failed trials of Alzheimer’ Dementia (AD) drugs.

Author(s):  
Ting Kang ◽  
Zhuang Miao ◽  
Siyu Liu ◽  
Bowen Ke

: Prodrug design is an effective method proven to improve the drug-like properties of a molecule, and it has been widely used in the drug development of various diseases. Due to the complexity of the central nervous system (CNS), the development of CNS drugs has high requirements related to the pharmaceutical, pharmacokinetic, and pharmacodynamic properties of the molecules. Prodrug design has now been widely and successfully applied to improve these properties. We conducted a mini-review to promote the use of the prodrug strategies in CNS drug development. To facilitate the description, we chose drug indications as a clue, then presented and discussed some representative CNS prodrugs. Finally, a brief summary and outlook about this area were presented.


2019 ◽  
pp. 303-314
Author(s):  
Fritz Zimprich

Patients with rare diseases face several common problems caused by the rarity of their diseases. Among many other issues, these include the often long-delayed diagnosis, the limited knowledge and dissemination of knowledge on the diseases, the lack of specific therapies, and the inadequacies of healthcare systems to deal with rare, complex disorders. In recent years patient advocacy organization have emerged for many different rare diseases as a consequence of these unmet needs. They have started to address these issues by many different advocacy actions such as education, political advocacy, and measures to facilitate research and drug development. Successful examples have shown that such efforts can bring real advances for some rare diseases.


2020 ◽  
Vol 21 ◽  
Author(s):  
Aashish Sharma ◽  
Romila Manchanda ◽  
Faheem Hyder Pottoo ◽  
Ghulam Md. Ashraf

: Impressive research steps have been taken for the treatment of neurological disorders in the last few decades. Still effective treatments of brain related disorders are very less due to problems associated with crossing the blood brain barrier (BBB), non-specific therapies, and delay in functional recovery of central nervous system (CNS) after treatment. Striving for novel treatment options for neurological disorders, nanotechnology-derived materials, and devices have gained the ground due to inherent features of derivatization/encapsulation with drugs as per the neurological ailments and pharmacological targets. Facile developments/syntheses of the nanomaterials-drug conjugates have also been the driving force for researchers to get into this field. Moreover, the tunable size and hydro/lipophilicity of these nanomaterials are the added advantages that make these materials more acceptable for CNS disorders. These nano-neurotherapeutics (NNTs) systems provide the platform for diagnosis, theranostics, treatments, restoration of CNS disorders, and encourage the translation of NNTs from “bench to bedside”. Still, these techniques are in primary stages of medical development. This review describes the latest advancements and future scenarios of developmental and clinical aspects of polymeric NNTs.


2018 ◽  
Vol 243 (14) ◽  
pp. 1125-1132 ◽  
Author(s):  
Jennifer L Wilson

An engineering perspective views cells as complex circuits that process inputs – drugs, environmental cues – to create complex outcomes – disease, growth, death – and this perspective has immense potential for drug development. Logical rules can describe the features of cells and reductionist approaches have exploited these rules for drug development. In contrast, the reductionist approach serially characterizes cellular components and develops a deep understanding of each component’s specific role. This approach underutilizes the full system of biomolecules relevant to disease pathology and drug effects. An engineering perspective provides the tools to understand and leverage the full extent of biological systems; applying both reverse and forward engineering, a strength of the engineering approach has demonstrated progress in advancing understanding of disease and drug mechanisms. Drug development lacks sufficient engineering specifications, or empirical models, of drug pharmacodynamic effects and future efforts to derive empirical models of drug effects will streamline this development. At this stage of progress, the scientist engineer is uniquely poised to solve problems in therapeutics related to modulating multiple diseases with a single or multiple therapeutic agents and identifying pharmacodynamics biomarkers with knowledge of drug pathways. This article underscores the value of these principles in an age where drug development costs are soaring and finding efficacious therapies is challenging. Impact statement Many untreated diseases are not monogenic and are instead caused by multiple genetic defects. Because of this complexity, computational, logical, and systems understanding will be essential to discovering novel therapies. The scientist engineer is uniquely disposed to use this type of understanding to advance therapeutic discovery. This work highlights benefits of the scientist engineer perspective and underscores the potential impact of these approaches for future therapeutic development. By framing the scientist engineer’s tool set and increasing awareness about this approach, this article stands to impact future therapeutic development efforts in an age of rising development costs and high drug attrition.


Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1730
Author(s):  
Masashi Fujitani ◽  
Yoshinori Otani ◽  
Hisao Miyajima

Neurotrophins (NTs) are one of the most characterized neurotrophic factor family members and consist of four members in mammals. Growing evidence suggests that there is a complex inter- and bi-directional relationship between central nervous system (CNS) disorders and cardiac dysfunction, so-called “brain–heart axis”. Recent studies suggest that CNS disorders, including neurodegenerative diseases, stroke, and depression, affect cardiovascular function via various mechanisms, such as hypothalamic–pituitary–adrenal axis augmentation. Although this brain–heart axis has been well studied in humans and mice, the involvement of NT signaling in the axis has not been fully investigated. In the first half of this review, we emphasize the importance of NTs not only in the nervous system, but also in the cardiovascular system from the embryonic stage to the adult state. In the second half, we discuss the involvement of NTs in the pathogenesis of cardiovascular diseases, and then examine whether an alteration in NTs could serve as the mediator between neurological disorders and heart dysfunction. The further investigation we propose herein could contribute to finding direct evidence for the involvement of NTs in the axis and new treatment for cardiovascular diseases.


2013 ◽  
Vol 1 (4) ◽  
Author(s):  
Antonio Claudio Tedesco ◽  
Andrielle Castilho-Fernandes ◽  
Tácila Gabriele Lopes

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