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Introduction The number of individuals worldwide with Alzheimer's disease (AD) is growing at a rapid rate. New treatments are urgently needed. We review the current pipeline of drugs in clinical trials for the treatment of AD. Methods We interrogated ClinicalTrials.gov, the federal registry of clinical trials to identify drugs in trials. Results There are 126 agents in 152 trials assessing new therapies for AD: 28 treatments in Phase 3 trials, 74 in Phase 2, and 24 in Phase 1. The majority of drugs in trials (82.5%) target the underlying biology of AD with the intent of disease modification; 10.3% are putative cognitive enhancing agents; and 7.1% are drugs being developed to reduce neuropsychiatric symptoms. Discussion This pipeline analysis shows that target biological processes are more diversified, biomarkers are more regularly used, and repurposed agents are being explored to determine their utility for the treatment of AD.

Introduction Drugs that prevent the onset, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed. Methods We searched ClinicalTrials.gov for all current Phase 1, 2 and 3 clinical trials for AD and mild cognitive impairment (MCI) attributed to AD. We created an automated computational database platform to search, archive, organize, and analyze the derived data. The Common Alzheimer's Disease Research Ontology (CADRO) was used to identify treatment targets and drug mechanisms. Results On the index date of January 1, 2023, there were 187 trials assessing 141 unique treatments for AD. Phase 3 included 36 agents in 55 trials; 87 agents were in 99 Phase 2 trials; and Phase 1 had 31 agents in 33 trials. Disease‐modifying therapies were the most common drugs comprising 79% of drugs in trials. Twenty‐eight percent of candidate therapies are repurposed agents. Populating all current Phase 1, 2, and 3 trials will require 57,465 participants. Discussion The AD drug development pipeline is advancing agents directed at a variety of target processes. HIGHLIGHTS There are currently 187 trials assessing 141 drugs for the treatment of Alzheimer's disease (AD). Drugs in the AD pipeline address a variety of pathological processes. More than 57,000 participants will be required to populate all currently registered trials.

Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i), or gliflozins, are a group of antidiabetic drugs that have shown improvement in renal and cardiovascular outcomes in patients with kidney disease, with and without diabetes. In this review, we will describe the different proposed mechanisms of action of SGLT2i. Gliflozins inhibit renal glucose reabsorption by blocking the SGLT2 cotransporters in the proximal tubules and causing glucosuria. This reduces glycemia and lowers HbA 1c by ~1.0%. The accompanying sodium excretion reverts the tubuloglomerular feedback and reduces intraglomerular pressure, which is central to the nephroprotective effects of SGLT2i. The caloric loss reduces weight, increases insulin sensitivity, lipid metabolism, and likely reduces lipotoxicity. Metabolism shifts toward gluconeogenesis and ketogenesis, thought to be protective for the heart and kidneys. Additionally, there is evidence of a reduction in tubular cell glucotoxicity through reduced mitochondrial dysfunction and inflammation. SGLT2i likely reduce kidney hypoxia by reducing tubular energy and oxygen demand. SGLT2i improve blood pressure through a negative sodium and water balance and possibly by inhibiting the sympathetic nervous system. These changes contribute to the improvement of cardiovascular function and are thought to be central in the cardiovascular benefits of SGLT2i. Gliflozins also reduce hepcidin levels, improving erythropoiesis and anemia. Finally, other possible mechanisms include a reduction in inflammatory markers, fibrosis, podocyte injury, and other related mechanisms. SGLT2i have shown significant and highly consistent benefits in renal and cardiovascular protection. The complexity and interconnectedness of the primary and secondary mechanisms of action make them a most interesting and exciting pharmacologic group.

INTRODUCTION New therapies to prevent or delay the onset of symptoms, slow progression, or improve cognitive and behavioral symptoms of Alzheimer's disease (AD) are needed. METHODS We interrogated clinicaltrials.gov including all clinical trials assessing pharmaceutical therapies for AD active in on January 1, 2024. We used the Common Alzheimer's Disease Research Ontology (CADRO) to classify the targets of therapies in the pipeline. RESULTS There are 164 trials assessing 127 drugs across the 2024 AD pipeline. There were 48 trials in Phase 3 testing 32 drugs, 90 trials in Phase 2 assessing 81 drugs, and 26 trials in Phase 1 testing 25 agents. Of the 164 trials, 34% (N = 56) assess disease‐modifying biological agents, 41% (N = 68) test disease‐modifying small molecule drugs, 10% (N = 17) evaluate cognitive enhancing agents, and 14% (N = 23) test drugs for the treatment of neuropsychiatric symptoms. DISCUSSION Compared to the 2023 pipeline, there are fewer trials (164 vs. 187), fewer drugs (127 vs. 141), fewer new chemical entities (88 vs. 101), and a similar number of repurposed agents (39 vs. 40). Highlights In the 2024 Alzheimer's disease drug development pipeline, there are 164 clinical trials assessing 127 drugs. The 2024 Alzheimer's disease drug development pipeline has contracted compared to the 2023 Alzheimer pipeline with fewer trials, fewer drugs, and fewer new chemical entities. Drugs in the Alzheimer's disease drug development pipeline target a wide array of targets; the most common processes targeted include neurotransmitter receptors, inflammation, amyloid, and synaptic plasticity. The total development time for a potential Alzheimer's disease therapy to progress from nonclinical studies to FDA review is approximately 13 years.

Introduction Alzheimer's disease (AD) represents a global health crisis. Treatments are needed to prevent, delay the onset, slow the progression, improve cognition, and reduce behavioral disturbances of AD. We review the current clinical trials and drugs in development for the treatment of AD. Methods We searched the governmental website clinicaltrials.gov where are all clinical trials conducted in the United States must be registered. We used artificial intelligence (AI) and machine learning (ML) approaches to ensure comprehensive detection and characterization of trials and drugs in development. We use the Common Alzheimer's Disease Research Ontology (CADRO) to classify drug targets and mechanisms of action of drugs in the pipeline. Results As of January 25, 2022 (index date for this study) there were 143 agents in 172 clinical trials for AD. The pipeline included 31 agents in 47 trials in Phase 3, 82 agents in 94 trials in Phase 2, and 30 agents in 31 trials in Phase 1. Disease‐modifying therapies represent 83.2% of the total number of agents in trials; symptomatic cognitive enhancing treatments represent 9.8% of agents in trials; and drugs for the treatment of neuropsychiatric symptoms comprise 6.9%. There is a diverse array of drug targets represented by agents in trials including nearly all CADRO categories. Thirty‐seven percent of the candidate agents in the pipeline are repurposed drugs approved for other indications. A total of 50,575 participants are needed to fulfill recruitment requirements for all currently active clinical trials. Discussion The AD drug development pipeline has agents representing a substantial array of treatment mechanisms and targets. Advances in drug design, outcome measures, use of biomarkers, and trial conduct promise to accelerate the delivery of new and better treatments for patients with AD. Highlights There are 143 drugs in the current Alzheimer's disease (AD) drug development pipeline. Disease‐modifying therapies represent 83.2% of the candidate treatments. Current trials require 50,575 participants who will donate 3,878,843 participant‐weeks to clinical trials. The biopharmaceutical industry sponsors 50% of all clinical trials including 68% of Phase 3 trials. Sixty‐three percent of Phase 3 trials and 46% of Phase 2 trials include non–North American clinical trial site locations indicating the global ecosystem required for AD drug development.

Repurposed drugs provide a rich source of potential therapies for Alzheimer’s disease (AD) and other neurodegenerative disorders (NDD). Repurposed drugs have information from non-clinical studies, phase 1 dosing, and safety and tolerability data collected with the original indication. Computational approaches, “omic” studies, drug databases, and electronic medical records help identify candidate therapies. Generic repurposed agents lack intellectual property protection and are rarely advanced to late-stage trials for AD/NDD. In this review we define repurposing, describe the advantages and challenges of repurposing, offer strategies for overcoming the obstacles, and describe the key contributions of repurposing to the drug development ecosystem. Repurposed drugs provide a rich source of potential therapies for Alzheimer’s disease (AD) and other neurodegenerative disorders (NDD). In this review, the authors discuss the advantages and challenges of repurposing, offer strategies for overcoming the obstacles and describe the key contributions of repurposing to drug development.

The popularity of ready-to-eat (RTE) salads has prompted novel technology to prolong the shelf life of their ingredients. Fresh-cut romaine lettuce is widely used in RTE salads; however, its tendency to quickly discolor continues to be a challenge for the industry. Selecting the ideal lettuce accessions for use in RTE salads is essential to ensure maximum shelf life, and it is critical to have a practical way to assess and compare the quality of multiple lettuce accessions that are being considered for use in fresh-cut applications. Thus, in this work we aimed to determine whether a computer vision system (CVS) composed of image acquisition, processing, and analysis could be effective to detect visual quality differences among 16 accessions of fresh-cut romaine lettuce during postharvest storage. The CVS involved a post-capturing color correction, effective image segmentation, and calculation of a browning index, which was tested as a predictor of quality and shelf life of fresh-cut romaine lettuce. The results demonstrated that machine vision software can be implemented to replace or supplement the scoring of a trained panel and instrumental quality measurements. Overall visual quality, a key sensory parameter that determines food preferences and consumer behavior, was highly correlated with the browning index, with a Pearson correlation coefficient of −0.85. Other important sensory decision parameters were also strongly or moderately correlated with the browning index, with Pearson correlation coefficients of −0.84 for freshness, 0.79 for off odor, and 0.57 for browning. The ranking of the accessions according to quality acceptability from the sensory evaluation produced a similar pattern to those obtained with the CVS. This study revealed that multiple lettuce accessions can be effectively benchmarked for their performance as fresh-cut sources via a CVS-based method. Future opportunities and challenges in using machine vision image processing to predict consumer preferences for RTE salad greens is also discussed.

Background Drug development for neurodegenerative disorders (NDDs) is a long, complex, and expensive enterprise. Methods to optimize drug development for NDDs are needed. Basket trials have been widely used in oncology and have been promoted by the Food and Drug Administration as a means of enhancing the efficiency of drug development. Discussion We reviewed clinical trials for NDDs registered on clinicaltrials.gov in the past 10 years. We identified 59 basket trials assessing the impact of treatment on more than one NDD in the trial. Forty-one of the trials were for 25 agents addressing symptoms of NDD such as motor impairment, hypotension, or psychosis. Eighteen of the trials assessed 14 disease-modifying therapies; the principal targets were mitochondrial function, tau biology, or alpha-synuclein aggregation. Basket trials are most common in phase 2 but have been conducted in phase 1, phase 3, and phase 4. The duration and size of the basket trials are highly variable depending on their developmental phase and the intent of the trial. Parkinson’s disease was the most common disorder included in basket trials of symptomatic agents, and Alzheimer’s disease was the most common disorder included in basket trials of disease-modifying therapies. Most of the basket trials of symptomatic agents were sponsored by pharmaceutical companies (29 of 41 trials); similarly, most of the basket trials investigating DMTs in basket trials were sponsored by the biopharmaceutical industry (11/17 trials). Conclusions Basket trials may increase drug development efficiency by reducing redundancy in trial implementation, enhancing recruitment, sharing placebo groups, and using biomarkers relevant to the mechanism of action of the treatment across NDDs. There have been relatively few basket trials including multiple NDDs in the same trial conducted over the past 10 years. The use of the basket trial strategy may represent an opportunity to increase the efficiency of development programs for agents to treat NDDs.

Fresh-cut romaine lettuce’s high perishability challenges ready-to-eat (RTE) salad production. Selecting cultivars less prone to browning and decay is crucial for extending shelf life. Traditional quality evaluation methods using instrumentation and trained panelists are time-consuming and logistically complex. This study investigated the effectiveness of untrained volunteers in assessing fresh-cut romaine lettuce quality. Given that the average consumer in the USA is familiar with the flavor characteristics of romaine lettuce, this study proposed to investigate the value of having untrained volunteers discern the quality of fresh-cut romaine lettuce. Therefore, six romaine lettuce accessions (Green Forest, King Henry, Parris Island Cos, PI 491224, SM13-R2, and Sun Valley) were assessed for sensory quality attributes (browning, green color, decay, and overall quality) and compared with instrumentation analyses (gas composition including O2 and CO2, electrolyte leakage, and color). The results showed significant quality differences (p < 0.05) among the accessions, with some seasonal variability. Very importantly, the consumers’ (n = 159) assessments revealed similar results to those produced by either instrumentation or a trained panel. The consumers provided sensory scores that allowed for the grouping of accessions based on their postharvest quality, which efficiently matched their pedigree relationship. In conclusion, ad hoc consumer panels can be an effective way to characterize the quality of romaine lettuce for RTE salads.

Pterygoplichthys disjunctivus, locally named the armoured catfish, is a by-catch of tilapia fishing that accounts for up to 80% of total captured fish in the Adolfo Lopez Mateos dam, in Michoacán, México, affecting the economy of its surrounding communities. This invasive fish is discarded by fishermen since native people do not consume it, partly due to its appearance, yet it is rich in protein. The aim of this study was to produce hydrolysates from armoured catfish using food-grade proteases (neutrases HT and PF and alcalase PAL) and investigate the processing conditions (pH and temperature) that lead to a high degree of hydrolysis, antioxidant activity, and Angiotensin I-Converting Enzyme (ACE) Inhibitory activity. No other similar research has been reported on this underutilized fish. The antioxidant activity was measured by three different methods, ABTS, FRAP and ORAC, with relevance to food and biological systems in order to obtain a more comprehensive assessment of the activity. In addition, the main peptide sequences were identified. All enzymes produced hydrolysates with high antioxidant activity. In particular, the protease HT led to the highest antioxidant activity according to the ABTS (174.68 μmol Trolox equivalent/g fish) and FRAP (7.59 mg ascorbic acid equivalent/g fish) methods and almost the same as PAL according to the ORAC method (51.43 μmol Trolox equivalent/g fish). Moreover, maximum activity was obtained at mild pH and temperature (7.5; 50 °C). Interestingly, the ORAC values obtained here were higher than others previously reported for fish hydrolysates and similar to those reported for fruits such as blueberries, apples and oranges. The peptide sequence IEE(E) was present in several peptides in both hydrolysates; this sequence may be partly responsible for the high antioxidant activity, particularly the one based on iron-reducing power. These findings will be relevant to the valorization of other fish/fish muscle discards and could contribute to the production of food supplements and nutraceuticals.