scholarly journals Precision Neurology for Parkinson’s Disease: Coupling Miro1‐Based Diagnosis With Drug Discovery

2020 ◽  
Vol 35 (9) ◽  
pp. 1502-1508 ◽  
Author(s):  
Vinita Bharat ◽  
Xinnan Wang
2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.


MedChemComm ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 867-879 ◽  
Author(s):  
Urmila Maitra ◽  
Lukasz Ciesla

The review provides an overview of discovery of new drug leads from natural extracts usingDrosophilaas a screening platform to evaluate the therapeutic potential of phytochemicals against Parkinson's disease.


Author(s):  
Mikael C. O. Englund ◽  
Christopher L. R. Barratt

Ever since the first human embryonic stem cells (hES) were successfully derived and propagated in 1998 (1), an obvious topic of discussion has been the development of novel therapies based on stem cell technology for a number of diseases and conditions. Targets could include type 1 diabetes, Alzheimer’s disease, spinal cord injury, and Parkinson’s disease to name a few. hES cells can also be used for tissue engineering, to replace for example bone and cartilage, and for drug discovery. Exciting proof of principal experiments in animals demonstrate the clinical potential in this field. For example, in a rat model of Parkinson’s disease, dopamine neural grafts derived from mouse Es cells showed long-term survival, the production of dopamine and, importantly, persistent improvements in movement behaviour (2). The promises of these potential treatments is enormous. However, there are many hurdles to overcome before a therapy based on stem cells is a clinical reality. We outline (A) the variety of methods to derive hES cells including somatic cell nuclear transfer (SCNT) and describe the challenges and possible avenues of further use; (B) discuss the development of clinical grade hES cells and their use in the drug discovery process; and (C) alternative strategies to patient specific therapy including induced adult pluripotent stem cells (iPS cells).


Author(s):  
El-Shorbagi Abdel-Nasser ◽  
Chaudhary Sachin ◽  
Alshemali Khadeja A. ◽  
Alabdulrazzaq Razan F. ◽  
Alqahtani Fatma Y.

2018 ◽  
Vol 243 (13) ◽  
pp. 1037-1045 ◽  
Author(s):  
Abigail L Walker ◽  
Syed Z Imam ◽  
Ruth A Roberts

The discovery and development of new drugs are vital if we are to improve and expand treatment options available to improve outcomes for patients. Overall, therapeutic strategies fall into two broad categories: small molecules and biologics, although more recently there has been a growth in novel platforms such as miRNAs and oligonucleotides. On average, the development of a small molecule drug takes around 12 years and costs around $50m. Despite this huge investment of time and money, attrition remains a major challenge and very few molecules actually make it through to the market. Here, we look at reasons for attrition in the small molecule field with a focus on neurotoxicology and efforts being made to improve success via the development of imaging and fluidic biomarkers. We also look at learnings from other models of CNS damage and degeneration such as Parkinson’s disease, traumatic brain injury, and multiple sclerosis since these may offer the opportunity to improve tools available to nonclinical toxicologists in the early detection of potential neurotoxicity. Reciprocally, learnings from studies of animal neurotoxicity may offer better ways to potentially monitor patients during clinical development of new drugs for neurodegeneration. Impact statement Attrition in drug discovery and development remains a major challenge. Safety/toxicity is the most prevalent reason for failure with cardiovascular and CNS toxicities predominating. Non-invasive biomarkers of neurotoxicity would provide significant advantage by allowing earlier prediction of likely neurotoxicity in preclinical studies as well as facilitating clinical trials of new therapies for neurodegenerative conditions such as Parkinson’s disease (PD) and multiple sclerosis (MS).


2018 ◽  
Vol 13 (3) ◽  
pp. 229-239 ◽  
Author(s):  
Ines Trigo-Damas ◽  
Natalia Lopez-Gonzalez del Rey ◽  
Javier Blesa

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