Search

Single-cell multiomics (sc-multiomics) is a burgeoning field that simultaneously integrates multiple layers of molecular information, enabling the characterization of dynamic cell states and activities in development and disease as well as treatment response. Studying drug actions and responses using sc-multiomics technologies has revolutionized our understanding of how small molecules intervene for specific cell types in cancer treatment and how they are linked with disease etiology and progression. Here, we summarize recent advances in sc-multiomics technologies that have been adapted and improved in drug research and development, with a focus on genome-wide examination of drug-chromatin engagement and the applications in drug response and the mechanisms of drug resistance. Furthermore, we discuss how state-of-the-art technologies can be taken forward to devise innovative personalized treatment modalities in biomedical research.

Heme oxygenase (HO-2) is an enzyme mainly involved in the physiologic turnover of heme and intracellular gas sensing, and it is very abundant in the brain, testes, kidneys and vessels. Since 1990, when HO-2 was discovered, the scientific community has underestimated the role of this protein in health and disease, as attested by the small amount of articles published and citations received. One of the reason that have contributed to the lack of interest in HO-2 was the difficulty in upregulating or inhibiting this enzyme. However, over the last 10 years, novel HO-2 agonists and antagonists have been synthesized, and the availability of these pharmacological tools should increase the appeal of HO-2 as drug target. In particular, these agonists and antagonists could help explain some controversial aspects, such as the neuroprotective versus neurotoxic roles of HO-2 in cerebrovascular diseases. Furthermore, the discovery of HO-2 genetic variants and their involvement in Parkinson's disease, in particular in males, opens new avenues for pharmacogenetic studies in gender medicine. [ABSTRACT FROM AUTHOR]

Heme oxygenase (HO-2) is an enzyme mainly involved in the physiologic turnover of heme and intracellular gas sensing, and it is very abundant in the brain, testes, kidneys and vessels. Since 1990, when HO-2 was discovered, the scientific community has underestimated the role of this protein in health and disease, as attested by the small amount of articles published and citations received. One of the reason that have contributed to the lack of interest in HO-2 was the difficulty in upregulating or inhibiting this enzyme. However, over the last 10 years, novel HO-2 agonists and antagonists have been synthesized, and the availability of these pharmacological tools should increase the appeal of HO-2 as drug target. In particular, these agonists and antagonists could help explain some controversial aspects, such as the neuroprotective versus neurotoxic roles of HO-2 in cerebrovascular diseases. Furthermore, the discovery of HO-2 genetic variants and their involvement in Parkinson’s disease, in particular in males, opens new avenues for pharmacogenetic studies in gender medicine.

Regulatory agencies installed orphan drug regulations to stimulate research and development of new innovative treatments for life-threatening diseases with a low prevalence (rare diseases). We established a list of well-known food-related ingredients with clinical evidence for rare diseases in the open medical literature that obtained marketing authorization as an expensive "orphan drug", protected by intellectual property (IP) rights. We show that these ingredients are part of an established practice of medicinal compounding—a form of point of care manufacturing. We argue that these ingredients should be considered as "pharmaceutical commons", and that regulatory incentives for private companies and market protection mechanisms such as IP rights are not justified in this case. [ABSTRACT FROM AUTHOR]

In mainland China, there remains a shortage of pediatric drugs. The Chinese government has recently launched policies and incentives to encourage pediatric drug development and clinical trials. However, data on the characteristics or development trends of these trials are limited. In this review, we extracted source data from the Chinese Clinical Trials Registry and Information Transparency Platform and systematically reviewed the pediatric clinical trials conducted in mainland China from 2009 to 2020, a comprehensive process evaluation of the pediatric drug clinical trials development in the past decade, providing data support to policy makers and industry stakeholders. We included 487 pediatric clinical trials. Over the past decade, the number of pediatric trials has increased, especially since 2016. The most common therapeutic areas were infectious diseases (n = 108, 22.2%), agents for preventive purpose (n = 99, 20.3%), and neurological and psychiatric diseases (n = 71, 14.6%). The number of clinical trials involving epilepsy (39, 10.1%), asthma (33, 8.5%), and influenza (24, 6.2%) were the highest. The distribution of leading institutions is unbalanced in mainland China, with most units in East China (34.0%) and few in Southwest China (6.9%). China has made progress in improving the research and development environment of pediatric drugs and increasing pediatric trials. However, a wide gap in pediatric drug development and clinical trials quality exists between China and the developed countries. The pharmaceutical industry in China has faced grim setbacks, including study duplication, lack of innovation, poor research design, and unbalanced resource allocation. Thus, we suggest that the Chinese government should adjust their policies to improve innovation and clinical design capacity, and optimize resource allocation between regions.

Regulatory agencies installed orphan drug regulations to stimulate research and development of new innovative treatments for life-threatening diseases with a low prevalence (rare diseases). We established a list of well-known food-related ingredients with clinical evidence for rare diseases in the open medical literature that obtained marketing authorization as an expensive “orphan drug”, protected by intellectual property (IP) rights. We show that these ingredients are part of an established practice of medicinal compounding—a form of point of care manufacturing. We argue that these ingredients should be considered as “pharmaceutical commons”, and that regulatory incentives for private companies and market protection mechanisms such as IP rights are not justified in this case.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive and irreversible worsening of cognitive functions, inability to perform everyday activities, and mood disorders. As recently reported by [5], 132 drugs are under clinical development for AD and only 28 of them are in phase III; among these latter, nine are anti-amyloid agents, eight are compounds targeting neuropsychiatric symptoms, and only three are antioxidant/neurotransmitter-based therapies. Over the last few years, many drugs, initially authorized and marketed for the treatment of other diseases, have proven to be potentially effective for the treatment of AD. Decoding the synaptic dysfunction of bioactive human AD brain soluble A to inspire novel therapeutic avenues for Alzheimer's disease. [Extracted from the article]

An introduction to the journal is presented wherein the editor discusses various reports published within the issue including one on the importance of having predictive preclinical models for the proper study of Alzheimer's disease (AD) by P.R. Davis and E. Head, a study by Trovato Salinaro et al which highlights the link between the pathogenesis of AD and other diseases like glaucoma and another by C. Cornelius which examines the factors considered as common denominator of AD and osteoporosis.