Therapeutic drug repositioning with special emphasis on neurodegenerative diseases: Threats and issues

Abstract

Drug repositioning or repurposing is the process of discovering leading-edge indications for authorized or declined/abandoned molecules for use in different diseases. This approach revitalizes the traditional drug discovery method by revealing new therapeutic applications for existing drugs. There are numerous studies available that highlight the triumph of several drugs as repurposed therapeutics. For example, sildenafil to aspirin, thalidomide to adalimumab, and so on. Millions of people worldwide are affected by neurodegenerative diseases. According to a 2021 report, the Alzheimer’s disease Association estimates that 6.2 million Americans are detected with Alzheimer’s disease. By 2030, approximately 1.2 million people in the United States possibly acquire Parkinson’s disease. Drugs that act on a single molecular target benefit people suffering from neurodegenerative diseases. Current pharmacological approaches, on the other hand, are constrained in their capacity to unquestionably alter the course of the disease and provide patients with inadequate and momentary benefits. Drug repositioning–based approaches appear to be very pertinent, expense- and time-reducing strategies for the enhancement of medicinal opportunities for such diseases in the current era. Kinase inhibitors, for example, which were developed for various oncology indications, demonstrated significant neuroprotective effects in neurodegenerative diseases. This review expounds on the classical and recent examples of drug repositioning at various stages of drug development, with a special focus on neurodegenerative disorders and the aspects of threats and issues viz. the regulatory, scientific, and economic aspects.

Synergistic Approaches in Neurodegenerative Therapeutics: Multi-Target Drug Innovative Interventions for Alzheimer’s Disease

“…The quest for a deeper understanding of neurodegenerative mechanisms and identifying new biomarkers and therapeutic targets is crucial in reducing their impact. Drug discovery in the context of neurodegenerative diseases is complex, demanding a deep knowledge of disease mechanisms, thorough testing, and innovative treatment strategies [4]. Recently, there has been a shift towards more creative and comprehensive approaches in drug discovery, utilizing advancements in Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s).…”

A case-control study of phosphodiesterase-5 inhibitor use and Alzheimer’s disease and related dementias among male and female patients aged 65 years and older supporting the need for a phase III clinical trial

“…Recently, there has been a push for research into repurposing existing FDA-approved drugs to treat and/or prevent AD, because the safety profiles of the drugs have already been established [ 19 , 20 ]. The phosphodiesterase inhibitors are one such class of drugs.…”

Synthesis of Veliparib Prodrugs and Determination of Drug-Release-Dependent PARP-1 Inhibition

“…Neuronal cell death manifests itself in cognitive dysfunction, motor impairment, and behavioral alteration, giving rise to neuro­degenerative diseases and dementia. , Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and traumatic brain injury (TBI) already affect millions of people worldwide, and dementia threatens to become the most common human disease at the time of death. , …”

“…1,2 Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and traumatic brain injury (TBI) already affect millions of people worldwide, and dementia threatens to become the most common human disease at the time of death. 3,4 Mitochondrial dysfunction is a shared hallmark of aging and neurodegeneration caused by persistent oxidative stress and increased mitochondrial Ca 2+ uptake, leading to the impairment of the electron transport chain and a decrease in ATP production. 5,6 Considerable efforts have been made to identify the key molecular determinants for these pathogenic events, and several candidates have been identified.…”

“… 1 , 2 Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and traumatic brain injury (TBI) already affect millions of people worldwide, and dementia threatens to become the most common human disease at the time of death. 3 , 4 …”