Screening Technologies Research Articles

The Excess of Carriers in Rare Disorders Suggests a Nonpathogenic Effect for Most Variants of Uncertain Significance.

Functional annotation and interpretation of genetic variants are a critical step in genetic diagnosis, as it may lead to personalized therapeutic options and genetic counseling. While the number of confirmed pathogenic genetic variants in an individual is relatively low, the number of variants of uncertain significance (VOUS) can be considerably higher, increasing the number of potential carriers of genetic disorders. Thus, reducing uncertainty and assessing the real effect of VOUS are crucial for clinical and medical genetics. In this study, we evaluated the efficacy of genetic screening technologies in accurately predicting pathogenic variants and their corresponding disease prevalence in a cohort of over 6000 healthy individuals involved in assisted reproduction programs. Using data from 305 genes associated with recessive disorders, we determined the frequency of carriers of pathogenic variants and VOUS in our dataset and compared the predicted prevalence based on this information with reported population prevalence data. The higher predicted prevalence in some disorders when considering VOUS suggests a mostly benign effect.

Health technology assessment of nailfold capillaroscopy and digital retina imaging in diabetes screening

AimThis study aims to identify the criteria for the evaluation of medical technologies in diabetes screening and then perform health technology assessment (HTA) for two technologies: digital retina imaging (DRI) and Nailfold Capillaroscopy (NFC). MethodsA multicriteria decision-making tool measuring attractiveness using a categorical-based evaluation technique (MACBETH) was used to calculate and compare alternatives. A focus group of ten decision-makers with more than ten years of experience in health technology was used for the decision-making. The Delphi Method was used to get a consensus about comparing criteria and alternatives to these criteria. The sampling method used in the study was the nonprobability purposive sampling method. ResultsThe study concluded that clinical efficacy (0.42) is the most important criterion for evaluating medical technologies, followed by cost-effectiveness (0.27). At the same time, ethical considerations were found to be less important (0.03). The sensitivity analysis concluded that the decision is sensitive to clinical efficacy and cost-effectiveness changes. The study found that none of the alternatives dominates others as an option for early detection of diabetes through vascular changes. LimitationsThis study primarily uses systemic literature review methods to identify criteria for evaluating alternatives. There may be additional criteria for evaluation. ConclusionThis study provides an approach for a multicriteria comparison of medical devices. The study findings are useful for public health professionals and health policymakers. Plain language summaryThis study assesses nailfold capillaroscopy (NFC) as a substitute for digital retina imaging (DRI) in diabetes screening using the MACBETH multicriteria decision-making tool. The research identifies five key evaluation criteria: clinical efficacy, cost-effectiveness, patient needs, user safety, and ethical considerations. A focus group of experienced health technology decision-makers was used to compare NFC and DRI. Results indicate that clinical efficacy and cost-effectiveness are the most critical factors, with NFC showing potential but not significantly outperforming DRI. Sensitivity analyses highlight the need for further research to validate NFC as an effective diabetes screening tool.

Examining the use of drug screening technologies in night-time entertainment districts

Examining the use of drug screening technologies in night-time entertainment districts

Prevalence and risk factors for blood-borne viruses among multi-transfused patients in Sana'a City, Yemen

Background: Blood-borne viruses (BBVs), like hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) among multi-transfused patients (MTPs), remain a major public health problem in Yemen. This study aimed to determine the seroprevalence of BBVs and associated risk factors among MTPs. Methods: A cross-sectional study was conducted on MTPs at the Yemeni Society for Thalassemia, National Oncology Center, and Al Kuwait University Hospital in Sana’a City. Data were collected through face-to-face interviews using a predesigned questionnaire. Blood samples were drawn and tested for HBsAg, anti-HCV, and HIV-1,2 by using an electrochemiluminescence immunoassay technique. Results: Among 361 MTPs, the overall seroprevalence of BBVs was 6.8%; seropositivity of HBsAg, anti-HCV, and anti-HIV-1,2 was 3.9%, 2.9%, and 0.0%, respectively. An increase in family size and low income were significantly associated factors with HBV infection. In addition, increases in age and blood transfusion units were found to be significant predictors for HCV (p<0.05). Conclusion: Although the seroprevalence of BBVs is low, it remains a major problem among MTPs. The most frequent infection was HBV, followed by HCV, with a significantly higher rate among leukemia patients. Regular mentoring for viral markers and mandatory implementation of HCV antigen-antibodies testing as well as advanced technology in blood screening are highly recommended.

Asymptomatic bacteriuria screening for developing countries using a modified water quality test kit.

Between 2% and 15% of pregnant women unknowingly experience asymptomatic bacteriuria (ASB), defined as ≥105 CFU per milliliter of urine in the absence of symptoms. ASB increases the risk of adverse pregnancy outcomes including pyelonephritis, preterm labor, and low-birth weight infants. While pregnant women in the United States are routinely screened for ASB, those in developing countries with limited resources and funding lack an accurate mechanism for ASB screening. Aquagenx water quality test kits detect Escherichia coli, the most common causative agent of ASB, and total coliform bacteria in drinking water via colorimetric and fluorescent indicators. We found that the Aquagenx system is compatible with human urine and then proceeded to develop an ASB screening protocol using disposable inoculating loops. Our protocol diagnosed artificial ASB- samples (104 CFU/mL E. coli) with a false positive (FP) rate of 33% (n = 18) and ASB+ (105 CFU/mL E. coli) with a false negative (FN) rate of 5.6% (n = 18). Clinical sample testing with our protocol revealed a FP rate of 0% in ASB- samples (n = 28) and a FN rate of 0% in ASB+ samples caused by coliforms (n = 13). Aquagenx did not detect ASB in nine clinical samples with non-coliform etiological agents due to the limitations of the technology. However, with very high accuracy for detection of E. coli and other causative agents that collectively account for 90.1% of ASB cases, these kits could be used as a diagnostic ASB screening tool in developing countries in which there is currently no alternative to urine culture.IMPORTANCEAsymptomatic bacteriuria (ASB) affects 2%-15% of pregnant women and can result in adverse maternal and fetal outcomes if left undetected and untreated. In the United States and other developed nations, pregnant women are regularly screened for ASB via urine culture. However, in low-resource countries where bacterial culture is not available, dipstick testing is used. Although accurate in cases of symptomatic bacteriuria, dipstick detection is ineffective for detecting ASB. Here, we made use of an existing water quality field test for ASB urine screening, which would be readily deployable in low-resource settings. We optimized a dilution protocol for sampling patient urine within the detection limits of the Aquagenx kit technology. Overall, we were able to detect ASB samples with Gram-negative pathogens that collectively account for 90% of all ASB cases. Utilization of this repurposed technology for proactive medical screening may help prevent adverse pregnancy and birth outcomes due to ASB.

Innovative Approach of High-Throughput Screening in the Drug Discovery Quest for Chronic Bronchitis Treatment

Chronic bronchitis (CB) is a challenging condition that worsens over time. Patients continue to experience an abundance of symptoms despite their best attempts to manage them. The etiology of CB is goblet cell overproduction and mucus hypersecretion, which aggravates airflow obstruction by luminal blockage of small airways, epithelial remodeling and modification of airway surface tension that predisposes to collapse. Larger randomized controlled trials are required to validate the pilot data that are currently accessible and assess the treatment’s durability as therapies are still in the early stages of clinical development. To overcome the prevailing increase in CB with the rise in air pollution globally, this study proposes a de novo drug discovery candidate for the effective treatment of CB. With the aid of cutting-edge technology of high-throughput screening, a phytochemical, apigenin, has been administered to target the Beta-2 adrenergic receptor protein and utilized as an exemplary ligand to target the discovery of a suitable drug candidate for Beta-2 adrenergic receptor protein. The drug likeness scores, no evident toxicity and binding affinity –9.092 kcal/mol the “CHEMBL294878” proves to be a potential drug candidate discovered for CB. A therapeutic drug specifically meant to treat CB can be developed with the help of the computational data provided by the research presented in this study.

Ratting on wildlife crime: training African giant pouched rats to detect illegally trafficked wildlife

The illegal wildlife trade (IWT) is one of the largest global crime economies, directly threatening species and their habitats, and biodiversity, and indirectly the global climate, and countries’ economies. Syndicates operating within the IWT are often involved in trafficking of humans, weapons, and drugs. IWT takes place in large scale through international ports, with wildlife being smuggled inside shipping containers. Current methods to combat IWT and screen these shipping containers, such as X-ray scans, are expensive and time-consuming. Scent-detection animals present an innovative approach to combatting IWT, as animals may be better suited to distinguish between organic materials and less susceptible to visual concealment methods. Previous scent-detection work has largely focused on conservation dogs (Canis lupus familiaris). Here, we present a series of proof-of-principle studies training African giant pouched rats (Cricetomys ansorgei) to detect illegally trafficked wildlife. As initial proof-of-principle within a controlled laboratory environment, we trained rats (n=11) to detect the scent of pangolin scales (Manis spp.) and a threatened African hardwood (Dalbergia melanoxylon). In subsequent experiments, we trained these rats (n=10) to detect rhinoceros horn (family Rhinocerotidae), and elephant tusks (Loxodonta spp.). At the conclusion of these studies, rats (n=7) accurately identified all four target species (although ivory samples may have been cross-contaminated, and results should be interpreted with caution) while correctly rejecting non-target items commonly used by traffickers to conceal the presence of illicit material. Rats detected the presence of wildlife targets even when these were concealed in mixtures among non-target items. These results provide the foundation to train rats for scent-detection of illegally trafficked wildlife to combat IWT. The unique attributes of rats could allow them to complement existing screening technologies in the fight against IWT. Rats have low training and maintenance costs, flexibly work with multiple handlers, have a long lifespan, and a sophisticated sense of smell. Their small size also offers unique capabilities for the screening of shipping containers, such as being able to navigate densely packed areas or be lifted to assess contents of sealed containers by screening ventilation systems. Future directions include assessing operational feasibility of deploying rats at ports.

Identification of Plasma Protein Biomarkers for Predicting Lung Cancer.

Lung cancer remains a leading cause of cancer-related mortality worldwide, necessitating the development of effective early diagnostic strategies. Despite advancements in imaging and screening technologies, late-stage diagnoses remain common, limiting treatment options and reducing survival rates. Thus, there is a critical need for reliable, minimally invasive biomarkers to improve early detection and patient outcomes. Plasma protein biomarkers offer promising potential for early lung cancer detection and continuous disease monitoring. This study explored the potential of specific plasma protein markers as early indicators of lung cancer. Plasma samples were collected from normal healthy individuals and lung cancer patients, and protein purification and analysis were conducted using LC-MS/MS. A mixed-effect model was applied to select lung cancer-related protein markers based on label-free relative quantification values. We identified 29 proteins with potential for early lung cancer diagnosis, including complement proteins (CFB, C3, C8G, C1QA, C1R, C6), orosomucoid proteins (ORM1, ORM2), ceruloplasmin (CP), alpha-1-B glycoprotein (A1BG), and others. These proteins play diverse roles in immune response, inflammation, and cell signaling, suggesting their relevance in lung cancer pathophysiology. Our findings suggest the potential of plasma proteins as early diagnostic biomarkers for lung cancer. Further validation in larger cohorts is needed to confirm their clinical utility. Integrating these biomarkers into existing diagnostic modalities could enhance early detection accuracy, leading to improved patient outcomes.

No Ear Left Behind: Wireless Earbuds for Low-Cost Hearing Screening

Hearing loss is particularly harmful for language acquisition and neuro-development if it is left undetected in early childhood. Newborn hearing screening technologies using otoacoustic emissions (OAE) rely on detecting soft sounds generated by a healthy cochlea. High-income countries like the United States frequently implement hearing screening programs for every child at birth. However, such universal hearing screening is significantly less common in low- and middle-income countries, partly due to the conventional wisdom that the test requires sensitive and expensive acoustic hardware that costs thousands of dollars. In our MobiSys paper[1], we present the first wireless earbud design for low-cost hearing screening. Our hardware-software system reliably performs hearing screening using low-cost acoustic hardware, while being in the form-factor of a wireless earbud (Figure. 1a,b). The earbud hardware is designed to work across a large age range from newborns to adults. By developing low-cost and open-source wearable technology, our work may help address global health inequities in hearing screening by democratizing these medical devices.

Feasibility of snapshot testing using wearable sensors to detect cardiorespiratory illness (COVID infection in India).

The COVID-19 pandemic has challenged the current paradigm of clinical and community-based disease detection. We present a multimodal wearable sensor system paired with a two-minute, movement-based activity sequence that successfully captures a snapshot of physiological data (including cardiac, respiratory, temperature, and percent oxygen saturation). We conducted a large, multi-site trial of this technology across India from June 2021 to April 2022 amidst the COVID-19 pandemic (Clinical trial registry name: International Validation of Wearable Sensor to Monitor COVID-19 Like Signs and Symptoms; NCT05334680; initial release: 04/15/2022). An Extreme Gradient Boosting algorithm was trained to discriminate between COVID-19 infected individuals (n = 295) and COVID-19 negative healthy controls (n = 172) and achieved an F1-Score of 0.80 (95% CI = [0.79, 0.81]). SHAP values were mapped to visualize feature importance and directionality, yielding engineered features from core temperature, cough, and lung sounds as highly important. The results demonstrated potential for data-driven wearable sensor technology for remote preliminary screening, highlighting a fundamental pivot from continuous to snapshot monitoring of cardiorespiratory illnesses.

Single-cell technology for drug discovery and development

The success rate of drug development today remains low, with long development cycles and high costs, especially in areas such as oncology, neurology, immunology, and infectious diseases. Single-cell omics, encompassing transcriptomics, genomics, epigenomics, proteomics, and metabolomics enable the analysis of gene expression profiles and cellular heterogeneity from the perspective of individual cells, offering a high-resolution view of their functional diversity. These technologies can help reveal disease mechanisms, drug target identification and validation, selection of preclinical models and candidate drugs, and clinical decision-making based on disease response to drugs, all at the single-cell level. The development of deep learning technology has provided a powerful tool for research in drug discovery based on single-cell techniques, which has evolved with the advent of large-scale public databases to predict drug responses and targets. In addition, traditional Chinese medicine (TCMs) research has also entered the era of single-cell technology. Single-cell omics technologies offer an alternative way in deciphering the mechanisms of TCMs in disease treatment, revealing drug targets, screening new drugs, and designing combinations of TCMs. This review aims to explore the application of single-cell omics technologies in drug screening and development comprehensively, highlighting how they accelerate the drug development process and facilitate personalized medicine by precisely identifying therapeutic targets, predicting drug responsiveness, deciphering mechanisms of action. It is also concluded that drug development process and therapeutic efficacy of drugs can be improved by combining single-cell omics and artificial intelligence techniques.

Anti-OAcGD2 antibody in combination with ceramide kinase inhibitor mediates potent antitumor cytotoxicity against breast cancer and diffuse intrinsic pontine glioma cells.

O-acetylated GD2 (OAcGD2) is a cancer-related antigen that is currently being explored for therapeutic use. Exploring the intricate mechanisms behind OAcGD2 synthesis in cancer cells has long been a challenge. Leveraging state-of-the-art high-throughput RNAi screening and confocal imaging technologies, our study delves into the genetic network orchestrating OAcGD2 synthesis in breast cancer cells. By conducting a comprehensive siRNA screen targeting the OAcGD2 phosphatome/kinome, we identified 43 genetic modulators, with 25 downregulating and 18 upregulating OAcGD2 synthesis. Among these, our study focused on CERK, the gene-encoding ceramide kinase, a pivotal player in glycosphingolipid metabolism. Through meticulous experimentation utilizing anti-CERK inhibitor and siRNAs, we made a significant discovery: CERK inhibition robustly upregulates OAcGD2 in both neuroblastoma and breast cancer cells, concurrently dampening cell migration. Furthermore, our findings highlight an exciting prospect: augmenting the antibody-dependent cell cytotoxicity of the chimeric human/mouse anti-OAcGD2 IgG1 monoclonal antibody (c8B6 mAb) against breast cancer and diffuse intrinsic pontine glioma cell lines in combination with specific CERK inhibitors. These results underscore the pivotal role of CERK inhibition in bolstering OAcGD2 synthesis, thus, presenting a promising strategy to increase the efficacy of anti-OAcGD2-based immunotherapy in patients with neuroectodermal tumors. By shedding light on this intricate interplay, our study paves the way for innovative therapeutic strategies poised to revolutionize the treatment landscape for these aggressive malignancies.

Time on task effects during interactive visual search.

There is a major shift taking place in airports across the globe, changing from 2D dual-view X-ray screening to 3D computed tomography (CT) screening. 3D CT screening is believed to improve target detection since it enables screeners to interact with images of passenger baggage (i.e., rotating and zooming into the displays). The change in screening technology is moving what was once a purely visual search task to an interactive search task. Here, we conducted two experiments with a large sample size during February of 2023 (695 participants) to examine (a) changes in search performance between a simulated dual-view and simulated interactive search task and (b) the effects of time on task upon performance. Consistent with past research, we found that interactive search, when compared with dual-view search, produced higher response accuracy rates coupled with increased reaction times (RTs). However, while we found effects of time on task (RTs reduced, and participants became more likely to respond "absent" as the experiments progressed), there was no evidence that these effects differed across simulated dual-view and simulated interactive searches. The results are discussed in relation to benefits of interactive search for supporting target detection by airport screeners. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Public engagement with consumer sleep technology for obstructive sleep apnea screening: implications for equity, access, and practice.

To characterize public practices and perspectives on the use of consumer sleep technology (CST) and evaluate perspectives on using CST as a screening tool for obstructive sleep apnea (OSA). We designed a survey instrument incorporating content from validated instruments (STOP-BANG and the Epworth Sleepiness Scale) and hypothesis-generated questions. Survey development involved multidisciplinary collaboration among three board-certified sleep medicine experts, researchers, and consumers. The survey was disseminated across a national sample of adults living in the United States via an online platform. Among 897 respondents, the mean (SD) age was 47.5 (16.9) years; 73.1% were female, 81.8% were White, and 505 respondents (56.3%) reported having tracked sleep using CS. Factors associated with decreased odds of CST use included household income <$30,000 (OR 0.47, 95% CI 0.28-0.79; p=0.004), Medicaid insurance (OR 0.43, 95% CI 0.26-0.69; p=0.001), Medicare insurance (OR 0.59, 95% CI 0.41-0.84; p=0.004), and lack of a primary care physician (OR 0.55, 95% CI 0.33-0.91; p=0.021). Most respondents (91.1%) agreed or strongly agreed that screening for OSA would be a useful feature of CST, but respondents reporting an education of high school diploma or less (OR 0.48, 95% CI 0.29-0.79; p=0.004) were less likely to agree with this statement. Attitudes toward and use of CST differed based on demographic and socioeconomic factors. Further study is needed to understand and address barriers to CST adoption and to characterize implications for equitable access to care for sleep disorders.

Expert consensus on the clinical application strategy of NIPT2.0, a new-generation non-invasive prenatal screening technology

The new-generation non-invasive prenatal screening technology (NIPT2.0) is a new method successfully realized in recent years based on high-throughput sequencing to synchronously and accurately detect fetal chromosomal aneuploidies, microdeletion/microduplication syndromes and dominantly inherited monogenic disorders. NIPT2.0 can circumvent the shortcomings of previous non-invasive prenatal screening techniques (NIPT and NIPT Plus) including incapability to detect fetal monogenic disorders, insufficient accuracy of detection and low positive predictive values for certain chromosomal abnormalities (in particular trisomy 13, sex chromosomal abnormalities, and small-segment microdeletions and microduplication syndromes). How to apply NIPT2.0 reasonably and normatively to maximize its clinical value has become an issue which requires clarification. The Reproductive Health Branch of the Chinese Maternal and Child Health Care Association and the Genetic Diagnosis Branch of the Genetics Society of China have organized experts to fully discuss and jointly drafted this consensus, which has put forwards suggestions over the clinical application strategy for NIPT2.0, including the scope of application, target disease, pre-test consultation, clinical application pathway, post-test genetic counseling and intervention, quality control and limitations, for the reference by peers, with a view to standardize its application and provide better clinical service.

Reassessing Cervical Cancer Prevention: Evaluating the NHS Cervical Cancer Screening Programme Through the Health Belief Model and Global Health Promotion Strategies

Cervical cancer remains a significant public health issue in the United Kingdom, with disparities in screening coverage and outcomes persisting despite robust national programs. This critical analysis evaluates the NHS Cervical Screening Programme (CSP) through the lens of the Health Belief Model (HBM) and global health promotion strategies, such as those outlined in the Ottawa Charter. The analysis explores how individual beliefs about susceptibility, severity, benefits, and barriers influence participation in cervical screening, while also critiquing the CSP's reliance on these factors to the potential exclusion of broader social determinants of health. Key findings reveal that while the HBM provides a valuable framework for understanding individual health behaviors, its emphasis on personal responsibility may overlook significant socioeconomic and cultural barriers, leading to inequities in screening uptake. Furthermore, the CSP's approach, though well-intentioned, may inadvertently undermine patient autonomy by promoting a top-down model of health promotion. The analysis is supported by data from the 2022-2023 Cervical Screening Standards Data Report and other contemporary sources, highlighting the need for more culturally sensitive and equitable strategies. Recommendations for policymakers include the enhancement of targeted interventions for high-risk groups, improved communication strategies, and the integration of a social model of health that considers the broader determinants of health. Future studies are encouraged to explore the sociocultural factors influencing screening behaviors and to evaluate the effectiveness of new screening technologies and integrated HPV vaccination programs. This analysis underscores the importance of rethinking cervical cancer prevention strategies to ensure they are inclusive, equitable, and aligned with the principles of health promotion.

372 (PB360): Discovery of a highly MTA-synergistic series of PRMT5 inhibitors for the treatment of MTAP-deficient tumors by virtual screening technology

372 (PB360): Discovery of a highly MTA-synergistic series of PRMT5 inhibitors for the treatment of MTAP-deficient tumors by virtual screening technology

Exploring the Artificial Intelligence and Its Impact in Pharmaceutical Sciences: Insights Toward the Horizons Where Technology Meets Tradition.

The technological revolutions in computers and the advancement of high-throughput screening technologies have driven the application of artificial intelligence (AI) for faster discovery of drug molecules with more efficiency, and cost-friendly finding of hit or lead molecules. The ability of software and network frameworks to interpret molecular structures' representations and establish relationships/correlations has enabled various research teams to develop numerous AI platforms for identifying new lead molecules or discovering new targets for already established drug molecules. The prediction of biological activity, ADME properties, and toxicity parameters in early stages have reduced the chances of failure and associated costs in later clinical stages, which was observed at a high rate in the tedious, expensive, and laborious drug discovery process. This review focuses on the different AI and machine learning (ML) techniques with their applications mainly focused on the pharmaceutical industry. The applications of AI frameworks in the identification of molecular target, hit identification/hit-to-lead optimization, analyzing drug-receptor interactions, drug repurposing, polypharmacology, synthetic accessibility, clinical trial design, and pharmaceutical developments are discussed in detail. We have also compiled the details of various startups in AI in this field. This review will provide a comprehensive analysis and outline various state-of-the-art AI/ML techniques to the readers with their framework applications. This review also highlights the challenges in this field, which need to be addressed for further success in pharmaceutical applications.

A Triple-Mismatch Differentiating assay exploiting activation and trans cleavage of CRISPR-Cas12a for mutation detection with ultra specificity and sensitivity

Liquid biopsy technology is non-invasive and convenient, and is currently an emerging technology for cancer screening. Among them, clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein 12a (Cas12a) based nucleic acid detection technology has the advantages of high sensitivity, rapidity, and easy operation. However, CRISPR-Cas12a does not discriminate single-base mismatches of targets well enough to meet the needs of clinical detection. Herein, we developed the Triple-Mismatch Differentiating (TMD) assay. This assay amplified the small thermodynamic difference in mismatches at one site at the level of CRISPR-Cas12a activation to a significant thermodynamic difference at three sites at both the level of CRISPR-Cas12a activation and trans-cleavage, which greatly improves the ability of CRISPR-Cas12a to discriminate between base mismatches. Our manipulation greatly improved the specificity of the CRISPR-Cas12a system while maintaining its inherent sensitivity and simplicity, increasing the detection limit to 0.0001%. When testing samples from pancreatic cancer patients, our results were highly consistent with NGS sequencing results. We believe that the TMD assay will provide a new technology for early cancer detection and will be widely used in the clinical practice.

Findings from the individualized management of a patient with Acyl-CoA Oxidase-1 (ACOX1) deficiency: A bedside-to-bench-to-bedside strategy

Acyl-CoA Oxidase-1 (ACOX1) deficiency (MIM 264470) is an autosomal recessive disease characterized by impairments in the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, which is the first step in the catalysis of the β-oxidative breakdown of very long chain fatty acids (VLCFA) occuring in peroxisomes. The deleterious accumulation of VLCFA in several organs, including the brain, is a key biochemical feature of this disease which has devastating neurological consequences. ACOX1 deficiency is ultra-rare; as such, few studies have been conducted to determine the leading causes of symptoms or uncover new therapeutics. When confronted with one such case, we decided to bring drug discovery tools to the patient's bedside in an attempt to identify a cure. A skin biopsy was performed on a young patient with ACOX1 deficiency, following which screening technologies and mass spectrometry analysis techniques were applied to design a cellular assay that enabled the direct measurement of the effect of small molecules on the patient's primary fibroblasts. This approach is particularly well adapted to inherited metabolic disorders such as ACOX1 deficiency. Through the evaluation of a proprietary library of repurposable drugs, we found that the anthelmintic drug niclosamide led to a significant reduction in VLCFA in vitro. This drug was subsequently administered to the patient for more than six years. This study outlines the screening and drug selection processes. Additionally, we present our comprehensive clinical and biochemical findings that aided in understanding the patient's natural history and analysis of the progression of the patient's symptoms throughout the treatment period. Although the patient's overall lifespan was extended compared to the average age at death in severe early onset cases of ACOX1 deficiency, we did not observe any definitive evidence of clinical or biochemical improvement during niclosamide treatment. Nonetheless, our study shows a good safety profile of long-term niclosamide administration in a child with a rare neurodegenerative disease, and illustrates the potential of individualized therapeutic strategies in the management of inherited metabolic disorders, which could benefit both patients and the broader scientific and medical communities.