In search of innovative therapeutics for neuropsychiatric disorders: The case of neurodegenerative diseases

Abstract

The recent medical literature highlights the lack of new drugs able to prevent or treat neurodegenerative diseases such as Alzheimer disease or Parkinson disease. Yet, the prevalence of these diseases is growing, related to increasing life expectancy, and is leading to a rise in their economic and social cost. At the same time, pharmaceutical companies are reducing or halting their investment in neuropharmacological research. Why have advances in basic neuroscience and our understanding of these diseases not allowed innovative discoveries in drug research? This review will try to explain this failure and suggest possible solutions: develop basic and clinical research but with the emphasis on translational and truly collaborative research; improve preclinical studies by developing more appropriate animal models, using new biomarkers and methodologies such as imaging suitable for clinical trials, providing worthwhile information on the ability of the drug to reach its intended target and induce significant pharmacological changes; build a new system of research management, based on stronger interdisciplinary relations between preclinical and clinical research and including the introduction of international precompetitive research between academic teams, start-up companies and pharmaceutical laboratories; hold early discussions with the regulatory authorities during preclinical studies and at the beginning of clinical trials in order to validate the methodological approaches; involve patients' associations in this new organization of research. These changes should help to ensure the discovery of effective treatments for these pathologies.

Adenosine A2A Receptor Antagonists in Neurodegenerative Diseases: Huge Potential and Huge Challenges

“…With some exceptions of early-onset symptoms ( 24 ), age is the main factor for triggering the clinical symptoms ( 25 – 28 ). Whereas, Parkinson’s disease patients have successful dopamine-replacement therapies and other tools that may be used in the disease progression or to decrease the appearance of the medication side effects ( 29 – 31 ), Alzheimer’s disease patients have not yet got any really efficacious therapeutic drug/tool ( 32 , 33 ).…”

Neuro-Geriatrics

“…Neuro-Geriatrics is based on translational medicine with an emphasis on translating the most evolved research concepts into the practice of medicine [8,9]. Magnetic resonance imaging (MRI), fluorodeoxyglucose (FDG) positron emission tomography (PET), molecular imaging with amyloid-labeling ligands, electroencephalography (EEG), and electromyography (EMG) are all advanced technologies that contribute importantly to contemporary medicine.…”

Psychotropic Drug Development Strategies that Target Neuropsychiatric Etiologies in Alzheimer's and Parkinson's Diseases

“…Pharmacological treatment options that directly target cognitive impairment and/or neuropsychiatric symptoms in PD are limited [Connolly and Fox, ; Féger and Hirsch, ]. A few studies have examined the use of cholinesterase inhibitors such as rivastigmine [Darreh‐Shori and Jelic, ; Schrag et al, ] (a mixed butyrylcholinesterase and acetylcholinesterase inhibitor) and donepezil [Hasnain, ; Sawada and Oeda, ] in PD‐associated neuropsychiatric symptoms (Fig.…”