Comb Chem High Throughput Screen. 2022 Feb 10. doi: 10.2174/1386207325666220210125923. Online ahead of print.

ABSTRACT

BACKGROUND: As COVID-19 pandemic continues to affect people's lives, the government of India gave emergency use approval to the ayurvedic antimalarial drug Ayush-64 in April 2021 to treat asymptomatic COVID-19 positive and mild COVID-19 positive patients.

OBJECTIVE: This study aims to explore the therapeutic potential of Ayush-64 to treat COVID-19 and provide a new approach for repurposing Ayurvedic drugs.

METHODS: The bioactives present in Ayush-64 were found along with their targets, and a plantbioactive-target network was created. A protein-protein interaction network of the common targets of Ayush-64 and COVID-19 was constructed and analyzed to find the key targets of Ayush-64 associated with the disease. Gene ontology and pathway enrichment analysis were performed to find COVID-19 related biological processes and pathways involved by the key targets. The key bioactives were docked with SARS-CoV-2 main protease 3CL, native Human Angiotensin-converting Enzyme ACE2, Spike protein S1, and RNA-dependent RNA polymerase RdRp.

RESULTS: From the 336 targets for Ayush-64, we found 38 key targets. Functional enrichment analysis of the key targets resulted in 121 gene ontology terms and 38 pathways. When molecular docking was performed with four receptors, thirteen bioactives showed good binding affinity comparable to that of the eight drugs presently used to treat COVID-19.

CONCLUSION: Network pharmacological analysis and molecular docking study of Ayush-64 revealed that it can be recommended to treat COVID-19. Further in vitro and in vivo studies are needed to confirm the results. The study demonstrated a new approach for repurposing Ayurvedic drugs.

PMID:35142268 | DOI:10.2174/1386207325666220210125923

Front Chem. 2022 Jan 24;10:838063. doi: 10.3389/fchem.2022.838063. eCollection 2022.

NO ABSTRACT

PMID:35141200 | PMC:PMC8819009 | DOI:10.3389/fchem.2022.838063

Comput Math Methods Med. 2022 Jan 31;2022:6783659. doi: 10.1155/2022/6783659. eCollection 2022.

ABSTRACT

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease for which there is a lack of therapeutic options. Genome-wide association studies (GWASs) have identified over 100 genetic loci associated with RA susceptibility; however, the most causal risk genes (RGs) associated with, and molecular mechanism underlying, RA remain unknown. In this study, we collected 95 RA-associated loci from multiple GWASs and detected 87 candidate high-confidence risk genes (HRGs) from these loci via integrated multiomics data (the genome-scale chromosome conformation capture data, enhancer-promoter linkage data, and gene expression data) using the Bayesian integrative risk gene selector (iRIGS). Analysis of these HRGs indicates that these genes were indeed, markedly associated with different aspects of RA. Among these, 36 and 46 HRGs have been reported to be related to RA and autoimmunity, respectively. Meanwhile, most novel HRGs were also involved in the significantly enriched RA-related biological functions and pathways. Furthermore, drug repositioning prediction of the HRGs revealed three potential targets (ERBB2, IL6ST, and MAPK1) and nine possible drugs for RA treatment, of which two IL-6 receptor antagonists (tocilizumab and sarilumab) have been approved for RA treatment and four drugs (trastuzumab, lapatinib, masoprocol, and arsenic trioxide) have been reported to have a high potential to ameliorate RA. In summary, we believe that this study provides new clues for understanding the pathogenesis of RA and is important for research regarding the mechanisms underlying RA and the development of therapeutics for this condition.

PMID:35140805 | PMC:PMC8820924 | DOI:10.1155/2022/6783659

Front Microbiol. 2022 Jan 24;12:790686. doi: 10.3389/fmicb.2021.790686. eCollection 2021.

ABSTRACT

Because of the excessive use of antibiotics, methicillin-resistant Staphylococcus aureus (MRSA) has become prevalent worldwide. Moreover, the formation of S. aureus biofilms often cause persistence and relapse of infections. Thus, the discovery of antibiotics with excellent antimicrobial and anti-biofilm activities is urgently needed. In the present study, eltrombopag (EP), a classic thrombopoietin receptor agonist, exhibited potential antimicrobial activity against S. aureus and its biofilms. Through our mechanistic studies, EP was found to interfere with proton motive force in S. aureus. The in vivo anti-infective efficacy of EP was further confirmed in the wound infection model, thigh infection model and peritonitis model by MRSA infection. In addition, the cytotoxicity of EP against mammalian cells and the in vivo toxicity of EP in animal models were not observed at the tested concentrations. Collectively, these results indicate that EP could be considered a potential novel antimicrobial agent against recalcitrant infections caused by MRSA.

PMID:35140693 | PMC:PMC8819062 | DOI:10.3389/fmicb.2021.790686

Assay Drug Dev Technol. 2022 Feb 9. doi: 10.1089/adt.2022.002. Online ahead of print.

NO ABSTRACT

PMID:35138939 | DOI:10.1089/adt.2022.002

Arch Virol. 2022 Feb 9. doi: 10.1007/s00705-022-05368-z. Online ahead of print.

ABSTRACT

In the current pandemic of coronavirus disease 2019 (COVID-19), antiviral drugs are at the center of attention because of their critical role against severe acute respiratory disease syndrome coronavirus 2 (SARS-CoV-2). In addition to designing new antivirals against SARS-COV-2, a drug repurposing strategy is a practical approach for treating COVID-19. A brief insight about antivirals would help clinicians to choose the best medication for the treatment of COVID-19. In this review, we discuss both novel and repurposed investigational antivirals, focusing on in vitro, in vivo, and clinical trial studies.

PMID:35138438 | DOI:10.1007/s00705-022-05368-z

Curr Res Pharmacol Drug Discov. 2022 Feb 4:100086. doi: 10.1016/j.crphar.2022.100086. Online ahead of print.

ABSTRACT

Since its inception in late December 2020 in China, novel coronavirus has affected the global socio-economic aspect. Currently, the world is seeking safe and effective treatment measures against COVID-19 to eradicate it. Many established drug molecules are tested against SARS-CoV-2 as a part of drug repurposing where some are proved effective for symptomatic relief while some are ineffective. Drug repurposing is a practical strategy for rapidly developing antiviral agents. Drug repurposing typically begins with virtual screening of existing drugs using docking experiments. Many drugs are presently being repurposed utilizing basic understanding of disease pathogenesis and drug pharmacodynamics, as well as computational methods. In the present situation, drug repositioning could be viewed as a new treatment option for COVID-19. Several new drug molecules and biologics are engineered against SARS-CoV-2 and are under different stages of clinical development. A few biologics drug products are approved by USFDA for emergency use in the covid management. Due to continuous mutation, many of the approved vaccines are not much efficacious to render the individual immune against opportunistic infection of SARS-CoV-2. Hence, there is a strong need for the cogent therapeutic agent for covid management. In this review, a consolidated summary of the therapeutic development against SARS-CoV-2 is depicted along with an overview of effective management of post COVID-19 complications.

PMID:35136858 | PMC:PMC8813675 | DOI:10.1016/j.crphar.2022.100086

Bioinformatics. 2022 Feb 4:btac048. doi: 10.1093/bioinformatics/btac048. Online ahead of print.

ABSTRACT

MOTIVATION: Drug-target interaction prediction plays an important role in new drug discovery and drug repurposing. Binding affinity indicates the strength of drug-target interactions. Predicting drug-target binding affinity is expected to provide promising candidates for biologists, which can effectively reduce the workload of wet laboratory experiments and speed up the entire process of drug research. Given that numerous new proteins are sequenced and compounds are synthesized, several improved computational methods have been proposed for such predictions, but there are still some challenges. i. many methods only discuss and implement one application scenario, they focus on drug repurposing and ignore the discovery of new drugs and targets. ii. many methods do not consider the priority order of proteins (or drugs) related to each target drug (or protein). Therefore, it is necessary to develop a comprehensive method that can be used in multiple scenarios and focuses on candidate order.

RESULTS: In this study, we propose a method called NerLTR-DTA that uses the neighbor relationship of similarity and sharing to extract features, and applies a ranking framework with regression attributes to predict affinity values and priority order of query drug (or query target) and its related proteins (or compounds). It is worth noting that using the characteristics of learning to rank to set different queries can smartly realize the multi-scenario application of the method, including the discovery of new drugs and new targets. Experimental results on two commonly used datasets show that NerLTR-DTA outperforms some state-of-the-art competing methods. NerLTR-DTA achieves excellent performance in all application scenarios mentioned in this study, and the r2m(test) values guarantee such excellent performance is not obtained by chance. Moreover, it can be concluded that NerLTR-DTA can provide accurate ranking lists for the relevant results of most queries through the statistics of the association relationship of each query drug (or query protein). In general, NerLTR-DTA is a powerful tool for predicting drug-target associations and can contribute to new drug discovery and drug repurposing.

AVAILABILITY: The proposed method is implemented in Python and Java. Source codes and datasets are available at https://github.com/RUXIAOQING964914140/NerLTR-DTA.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35134828 | DOI:10.1093/bioinformatics/btac048

ChemMedChem. 2022 Feb 8:e202200053. doi: 10.1002/cmdc.202200053. Online ahead of print.

NO ABSTRACT

PMID:35132799 | DOI:10.1002/cmdc.202200053

Eur J Med Chem. 2022 Jan 28;231:114156. doi: 10.1016/j.ejmech.2022.114156. Online ahead of print.

ABSTRACT

Neural precursor cell expressed developmentally downregulated protein-8 (NEDD8) is a ubiquitin-like protein, which activates an important post-translational modification process: neddylation, thereby regulating the stability and degradation of various proteins related to multiple physiological processes. And the abnormal activation of NEDD8 (overexpression or underexpression) is related to the occurrence of multiple cancers including gastric carcinoma. NEDD8 activating enzyme (NAE), a key enzyme for the activation of NEDD8, controls the initiation of the NEDD8 transfer cascade, which is an important target for anti-tumor drugs. With the disclosure of the anti-tumor mechanism, NAE modulators (inhibitors and agonists) have gradually become a research hotspot in the development of anti-tumor drugs. And the application of NAE modulators has also been further expanded, not only limited to certain hematological tumors, its therapeutic potential in multiple solid tumors, especially gastric carcinoma, has been gradually uncovered. This paper mainly explains the structural characteristics, catalytic sites, and mechanism of NAE. And the relationships between neddylation and tumors are also elaborated from the perspective of NAE regulating the downstream pathways. In addition, the NAE modulators reported in recent years were reviewed, mainly focusing on their discovery processes, structure-activity relationships, inhibitory efficacy, pharmacological mechanism, and clinical research. And we reasonably predict the application of NAE modulators in gastric carcinoma, according to its relationship with neddylation. We summarize the issues in NAE modulator development and discuss the possible development directions.

PMID:35131538 | DOI:10.1016/j.ejmech.2022.114156

Eur J Pharmacol. 2022 Feb 4:174800. doi: 10.1016/j.ejphar.2022.174800. Online ahead of print.

ABSTRACT

Neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, are characterized by the progressive loss of neuronal cells, resulting in different clinical symptoms according to the affected brain region. Although there are drugs available for the treatment of these diseases, they present relatively low efficacy and are not capable of modifying the course of the disease or stopping its progression. In the field of drug development, drug repurposing could be an interesting strategy to search new therapeutic options against neurodegenerative diseases, since it involves lower costs and time for development. In this review, we discuss the search of new treatments for Alzheimer's and Parkinson's disease through drug repurposing. A focus was given to drugs that modulate neuroinflammation, since it represents a common point among neurodegenerative diseases and has been explored as a target for drug action.

PMID:35131314 | DOI:10.1016/j.ejphar.2022.174800

Biochem Biophys Rep. 2022 Mar;29:101225. doi: 10.1016/j.bbrep.2022.101225. Epub 2022 Jan 31.

ABSTRACT

The current novel corona virus illness (COVID-19) is a developing viral disease that was discovered in 2019. There is currently no viable therapeutic strategy for this illness management. Because traditional medication development and discovery has lagged behind the threat of emerging and re-emerging illnesses like Ebola, MERS-CoV, and, more recently, SARS-CoV-2. Drug developers began to consider drug repurposing (or repositioning) as a viable option to the more traditional drug development method. The goal of drug repurposing is to uncover new uses for an approved or investigational medicine that aren't related to its original use. The main benefits of this strategy are that there is less developmental risk and that it takes less time because the safety and pharmacologic requirements are met. The main protease (Mpro) of corona viruses is one of the well-studied and appealing therapeutic targets. As a result, the current research examines the molecular docking of Mpro (PDB ID: 5R81) conjugated repurposed drugs. 12,432 approved drugs were collected from ChEMBL and drugbank libraries, and docked separately into the receptor grid created on 5R81, using the three phases of molecular docking including high throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP). Based on docking scores and MM-GBSA binding free energy calculation, top three drugs (kanamycin, sulfinalol and carvedilol) were chosen for further analyses for molecular dynamic simulations.

PMID:35128086 | PMC:PMC8801302 | DOI:10.1016/j.bbrep.2022.101225

Front Cardiovasc Med. 2022 Jan 20;8:826529. doi: 10.3389/fcvm.2021.826529. eCollection 2021.

ABSTRACT

Vascular calcification is a cardiovascular disorder with no therapeutic options. We recently reported that o-octanoyltransferase (CROT) suppression can inhibit vascular calcification in vivo and in vitro through amelioration of mitochondrial function and fatty acid metabolism. Inhibiting calcification with a small molecule compound targeting CROT-associated mechanisms will be a promising non-invasive treatment of vascular calcification. Here we used a computational approach to search for existing drugs that can inhibit vascular calcification through the CROT pathway. For screening of the compounds that reduce CROT expression, we utilized the Connectivity Map encompassing the L1000 computational platform that contains transcription profiles of various cell lines and perturbagens including small molecules. Small molecules (n = 13) were identified and tested in human primary smooth muscle cells cultured in osteogenic media to induce calcification. Niclosamide, an FDA-improved anthelmintic drug, markedly inhibited calcification along with reduced alkaline phosphatase activity and CROT mRNA expression. To validate this compound in vivo, LDL receptor (Ldlr)-deficient mice fed a high fat diet were given oral doses of niclosamide (0 or 750 ppm admixed with diet) for 10 weeks. Niclosamide treatment decreased aortic and carotid artery calcification as determined by optical near infrared molecular imaging (OsteoSense680) and histological analysis. In addition, niclosamide improved features of fatty liver, including decreased cholesterol levels along with decreased Crot expression, while plasma total cholesterol levels did not change. Proteomic analysis of aortic samples demonstrated that niclosamide affected wingless/integrated (Wnt) signaling pathway and decreased runt-related transcription factor 2 (Runx2) expression, an essential factor for calcification. Our target discovery strategy using a genetic perturbation database with existing drugs identified niclosamide, that in turn inhibited calcification in vivo and in vitro, indicating its potential for the treatment of vascular calcification.

PMID:35127876 | PMC:PMC8811128 | DOI:10.3389/fcvm.2021.826529

Comput Struct Biotechnol J. 2022 Jan 29. doi: 10.1016/j.csbj.2022.01.024. Online ahead of print.

ABSTRACT

Drug-repurposing has been instrumental to identify drugs preventing SARS-CoV-2 replication or attenuating the disease course of COVID-19. Here, we identify through structure-based drug-repurposing a dual-purpose inhibitor of SARS-CoV-2 infection and of IL-6 production by immune cells. We created a computational structure model of the receptor binding domain (RBD) of the SARS-CoV-2 spike 1 protein, and used this model for in silico screening against a library of 6171 molecularly defined binding-sites from drug molecules. Molecular dynamics simulation of candidate molecules with high RBD binding-scores in docking analysis predicted montelukast, an antagonist of the cysteinyl-leukotriene-receptor, to disturb the RBD structure, and infection experiments demonstrated inhibition of SARS-CoV-2 infection, although montelukast binding was outside the ACE2-binding site. Molecular dynamics simulation of SARS-CoV-2 variant RBDs correctly predicted interference of montelukast with infection by the beta but not the more infectious alpha variant. With distinct binding sites for RBD and the leukotriene receptor, montelukast also prevented SARS-CoV-2-induced IL-6 release from immune cells. The inhibition of SARS-CoV-2 infection through a molecule binding distal to the ACE-binding site of the RBD points towards an allosteric mechanism that is not conserved in the more infectious alpha and delta SARS-CoV-2 variants.

PMID:35126884 | PMC:PMC8800171 | DOI:10.1016/j.csbj.2022.01.024

Front Pharmacol. 2022 Jan 19;12:772026. doi: 10.3389/fphar.2021.772026. eCollection 2021.

ABSTRACT

Background: Drug repurposing provides an effective method for high-speed, low-risk drug development. Clinical phenotype-based screening exceeded target-based approaches in discovering first-in-class small-molecule drugs. However, most of these approaches predict only binary phenotypic associations between drugs and diseases; the types of drug and diseases have not been well exploited. Principally, the clinical phenotypes of a known drug can be divided into indications (Is), side effects (SEs), and contraindications (CIs). Incorporating these different clinical phenotypes of drug-disease associations (DDAs) can improve the prediction accuracy of the DDAs. Methods: We develop Drug Disease Interaction Type (DDIT), a user-friendly online predictor that supports drug repositioning by submitting known Is, SEs, and CIs for a target drug of interest. The dataset for Is, SEs, and CIs was extracted from PREDICT, SIDER, and MED-RT, respectively. To unify the names of the drugs and diseases, we mapped their names to the Unified Medical Language System (UMLS) ontology using Rest API. We then integrated multiple clinical phenotypes into a conditional restricted Boltzmann machine (RBM) enabling the identification of different phenotypes of drug-disease associations, including the prediction of as yet unknown DDAs in the input. Results: By 10-fold cross-validation, we demonstrate that DDIT can effectively capture the latent features of the drug-disease association network and represents over 0.217 and over 0.072 improvement in AUC and AUPR, respectively, for predicting the clinical phenotypes of DDAs compared with the classic K-nearest neighbors method (KNN, including drug-based KNN and disease-based KNN), Random Forest, and XGBoost. By conducting leave-one-drug-class-out cross-validation, the AUC and AUPR of DDIT demonstrated an improvement of 0.135 in AUC and 0.075 in AUPR compared to any of the other four methods. Within the top 10 predicted indications, side effects, and contraindications, 7/10, 9/10, and 9/10 hit known drug-disease associations. Overall, DDIT is a useful tool for predicting multiple clinical phenotypic types of drug-disease associations.

PMID:35126114 | PMC:PMC8809407 | DOI:10.3389/fphar.2021.772026

Sarcoma. 2022 Jan 28;2022:7157507. doi: 10.1155/2022/7157507. eCollection 2022.

ABSTRACT

Aldehyde dehydrogenase 1A1 (ALDH) is a cancer stem cell marker highly expressed in metastatic cells. Disulfiram (Dis) is an FDA-approved antialcoholism drug that inhibits ALDH and has been studied as a candidate for drug repurposing in multiple neoplasia. Dis cytotoxicity in cancer cells has been shown to be copper-dependent, in part due to Dis's ability to function as a bivalent metal ion chelator of copper (Cu). The objectives of this research were to test ALDH expression levels and Cu concentrations in sarcoma patient tumors and human osteosarcoma (OS) cell lines with differing metastatic phenotypes. We also sought to evaluate Dis + Cu combination therapy in human OS cells. Intracellular Cu was inversely proportional to the metastatic phenotype in human OS cell lines (SaOS2 > LM2 > LM7). Nonmetastatic human sarcoma tumors demonstrated increased Cu concentrations compared with metastatic tumors. qPCR demonstrated that ALDH expression was significantly increased in highly metastatic LM2 and LM7 human OS cell lines compared with low metastatic SaOS2. Tumor cells from sarcoma patients with metastatic disease displayed significantly increased ALDH expression compared with tumor cells from patients without metastatic disease. Serum Cu concentration in canine OS versus normal canine patients demonstrated similar trends. Dis demonstrated selective cytotoxicity compared with human multipotential stromal cells (MSCs): Dis-treated OS cells demonstrated increased apoptosis, whereas MSCs did not. CuCl2 combined with Dis and low-dose doxorubicin resulted in a superior cytotoxic effect in both SaOS2 and LM7 cell lines. In summary, ALDH gene expression and Cu levels are altered between low and highly metastatic human OS cells, canine samples, and patient tumors. Our findings support the feasibility of a repurposed drug strategy for Dis and Cu in combination with low-dose anthracycline to specifically target metastatic OS cells.

PMID:35125923 | PMC:PMC8816591 | DOI:10.1155/2022/7157507

Pharmacol Res. 2022 Feb 3:106114. doi: 10.1016/j.phrs.2022.106114. Online ahead of print.

ABSTRACT

Metformin is the oldest and most commonly used first-line antidiabetic drug because of its good clinical efficacy, high safety, low cost and easy access. At the same time, in recent years, we have found that its role as a therapeutic drug is gradually expanding. A large number of basic studies have shown that metformin may become a promising attractive candidate for drug repurposing. Therefore, it is extremely beneficial to conduct an in-depth discussion on the main mechanism of metformin. As early as the 1950s, studies showed that metformin played a biological role by regulating mitochondria. Then, ground-breaking studies showed that metformin functions by inhibiting complex I in the mitochondrial respiratory chain. Although there are still many controversies about the key molecular targets of metformin, with the emergence of more and more evidence, it gradually came to be concluded that mitochondria play a central role in the application of metformin. Mitochondria are important fulcrums for cell functions. The exact mechanism of action in mitochondria of this pleiotropic anti-hyperglycaemic molecule is still unclear. This review article explores the core role of mitochondria in the pharmacological and toxicological effects of metformin, and summarises the mechanism of action if metformin in mitochondria. It also provides ideas and supporting evidence for the re-development and reuse of metformin as an old drug, as well as new insight into the treatment of human diseases.

PMID:35124206 | DOI:10.1016/j.phrs.2022.106114

Br J Clin Pharmacol. 2022 Feb 4. doi: 10.1111/bcp.15258. Online ahead of print.

ABSTRACT

AIMS: The COVID-19 pandemic is a global public health emergency and patients with diabetes mellitus (DM) are disproportionately affected, exhibiting more severe outcomes. Recent studies have shown that metformin is associated with improved outcomes in patients with COVID-19 and DM and may be a potential candidate for drug repurposing. We aimed to investigate the effects of metformin on outcomes in patients with COVID-19 and DM.

METHODS: Databases (PubMed, Scopus, Web of Science, EMBASE, Clinicaltrials.gov and Cochrane library) were searched up to April 10, 2021 for studies reporting data on metformin use in COVID-19 patients with DM. The risk of bias was assessed using the Newcastle-Ottawa scale. Certainty of evidence was rated using the GRADE approach. The primary outcome was mortality reported in odds ratio. A random-effects meta-analysis was carried out on both unadjusted and adjusted ORs. This study is registered with PROSPERO, CRD42020221842.

RESULTS: 2,916,231 patients from 32 cohort studies were included in the quantitative and qualitative synthesis. The meta-analysis showed that metformin was significantly associated with lower mortality in COVID-19 patients with DM in both unadjusted (OR 0.61 [95% CI: 0.53-0.71], p<0.00001, I2 = 70%) and adjusted (OR 0.78 [95% CI: 0.69-0.88], p<0.00001, I2 = 67%) models.

CONCLUSION: Poor outcomes in COVID-19 patients with DM can be attributed to inadequate glycaemic control and weakened immune responses. Metformin has multiple effects that can improve outcomes in patients with DM and our findings highlight a possible role of its use. However, robust randomised trials are needed to thoroughly assess its use.

PMID:35122284 | DOI:10.1111/bcp.15258

Bioorg Chem. 2022 Jan 30;120:105642. doi: 10.1016/j.bioorg.2022.105642. Online ahead of print.

ABSTRACT

Huntington's disease (HD) is a rare, incurable, inheritedneurodegenerative disorder manifested by chorea, hyperkinetic, and hypokinetic movements. The FDA has approved only two drugs, viz. tetrabenazine, and deutetrabenazine, to manage the chorea associated with HD. However, several other drugs are used as an off-label to manage chorea and other symptoms such as depression, anxiety, muscle tremors, and cognitive dysfunction associated with HD. So far, there is no disease-modifying treatment available. Drug repurposing has been a primary drive to search for new anti-HD drugs. Numerous molecular targets along with a wide range of small molecules and gene therapies are currently under clinical investigation. More than 200 clinical studies are underway for HD, 75% are interventional, and 25% are observational studies. The present review discusses the small molecule clinical pipeline and molecular targets for HD. Furthermore, the biomarkers, diagnostic tests, gene therapies, behavioral and observational studies for HD were also deliberated.

PMID:35121553 | DOI:10.1016/j.bioorg.2022.105642

Cell Stem Cell. 2022 Feb 3;29(2):189-208. doi: 10.1016/j.stem.2022.01.007.

ABSTRACT

It has been 15 years since the birth of human induced pluripotent stem cell (iPSC) technology in 2007, and the scope of its application has been expanding. In addition to the development of cell therapies using iPSC-derived cells, pathological analyses using disease-specific iPSCs and clinical trials to confirm the safety and efficacy of drugs developed using iPSCs are progressing. With the innovation of related technologies, iPSC applications are about to enter a new stage. This review outlines advances in iPSC modeling and therapeutic development for cardinal neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease.

PMID:35120619 | DOI:10.1016/j.stem.2022.01.007