NEUBOrg: Artificially Induced Pluripotent Stem Cell-Derived Brain Organoid to Model and Study Genetics of Alzheimer’s Disease Progression

Esmail, Sally; Danter, Wayne R.

doi:10.3389/fnagi.2021.643889

Cited by 14 publications

(13 citation statements)

References 43 publications

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“…The immediate predecessor of the current version V6.2, was used to successfully simulate a whole brain organoid (Esmail and Danter, 2021b). The primary objective of this project was to extend the capabilities of the evolving DeepNEU platform by evaluating the ability of the updated DeepNEU platform (V6.3) to (1) create and validate wild type lung simulations (aiLUNG-WT),…”

Section: Discussionmentioning

confidence: 99%

A novel artificial lung organoid for simulating a patient derived adenocarcinoma of lung for personalized oncology

Esmail¹,

Danter²

2021

Preprint

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Optimizing patient care based on precision oncology will inevitably become the standard of care. If we accept the principle that every persons’ cancer is different then the most effective therapies will have to be designed for the individual patient and for their tumors genetic profile. Access to tumor mutational profiling is now widely available but continues to be limited by cost and actionable information. For example, novel combinations of approved drugs are rarely considered. These considerations lead us to hypothesize that artificially induced Lung Adenocarcinoma (LUAD) derived lung organoids could provide a novel, alternate approach for LUAD disease modeling and large-scale targeted drug screening.In this project, we used data from a commercially available tumor mutation profile to generate and then validate the artificially induced LUAD-derived lung organoid simulations (aiLUNG-LUAD) to model LUAD and identify several drug combinations that effectively reverse the tumors’ genotypic and phenotypic features when compared with placebo. These results complement previous LUAD-derived lung organoids research and provide a novel and widely applicable cancer drug-screening approach for precision/individualized oncology.

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Section: Discussionmentioning

confidence: 99%

A novel artificial lung organoid for simulating a patient derived adenocarcinoma of lung for personalized oncology

Esmail¹,

Danter²

2021

Preprint

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“…AD is the most prevalent neurodegenerative disease in aging. It affects over 44 million patients worldwide but few treatments are currently available (Esmail & Danter, 2021). It also affects the family members of the patients who often take on the role of caregivers.…”

Section: Prevalence Of Admentioning

confidence: 99%

Recent Advances in Alzheimer’s Disease Treatments with Therapeutic Antibodies to Amyloid-β

Yang¹,

Bradford²

2022

J Stud Res

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Alzheimer's disease (AD) is one of the most prevalent and devastating neurodegenerative disorders which affects tens of millions of patients. It imposes significant physical, emotional, and financial burdens on patients, families, and society. Formation of Amyloid-β (Aβ) plaques from the accumulation of Aβ peptides in the cortex and hippocampal region is considered one of the fundamental neuropathological pillars of the disease. Pathological Aβ peptides are generated from its precursor protein through proteolysis. Four small molecule medications were approved by the U. S. Food and Drug Administration (FDA) since 1968 to treat the cognitive symptoms of AD, but they are not curative and have no effect on the development of AD. At least four anti-Aβ antibodies and dozens of other anti-Aβ small molecule agents have been evaluated in clinical trials in the past decades but none of them showed consistent clinical efficacy, presumably because they cannot remove Aβ plaques effectively enough or other reasons such as the patient selection and trial design. Despite the failures, more anti-Aβ antibodies are under development, aiming for more efficient Aβ plaques removal through selectively targeting Aβ oligomers. Among those aducanumab was approved by FDA in 2021 as the first drug to address the underlying biology of AD rather than the symptoms.

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“…The current research project advances our previous simulation of the APOE ε4 variant in the first AI based simulation of a whole brain organoid (aiWBO) [15]. An advanced version of the aiWBO developed in that project forms the CNS organoid component of the current aiHumanoid simulations (v8.3).…”

Section: Introductionmentioning

confidence: 99%

Tracing Alzheimer’s Genetic Footprints: A Pioneering Longitudinal Study Using Artificial Intelligence to Unravel Mutation- Driven Risks and Progression in Virtual Patients; Part 1 – The APOE genotypes

Danter

2024

Preprint

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Alzheimer's Disease (AD), the most common neurodegenerative disorder, presents a significant challenge for early detection and intervention due to its complex etiology involving genetic, environmental, and lifestyle factors. This study harnesses the innovative potential of artificial intelligence (AI) through the aiHumanoid platform to simulate AD progression. In this study, we focus on the impact of two APOE genotypes on disease development and progression. Our longitudinal virtual subject simulations, grounded in extensive medical literature and genetic information, explore the nuanced interplay between specific genetic variants, APOE ε3/4 and ε4/4, and their role in AD's heterogeneity. Despite the potential limitations associated with emerging technologies, including the translatability of AI simulations to real-world scenarios and the scope of genetic variants, this research provides key insights into early biomarkers and the progression patterns of AD. Future segments of this study (Part 2 and Part 3) will broaden the analysis to encompass a wider array of genetic factors and their interactions, enhancing the understanding of AD and paving the way for personalized intervention strategies. Ethical considerations surrounding the use of AI in medical research are acknowledged, emphasizing the need for responsible integration of technology in healthcare. Our findings underscore the transformative potential of AI in advancing AD research, offering a foundation for future studies aimed at refining diagnostic and therapeutic approaches through enhanced realism in simulations and a comprehensive exploration of genetic and environmental factors.

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NEUBOrg: Artificially Induced Pluripotent Stem Cell-Derived Brain Organoid to Model and Study Genetics of Alzheimer’s Disease Progression

Cited by 14 publications

References 43 publications

A novel artificial lung organoid for simulating a patient derived adenocarcinoma of lung for personalized oncology

A novel artificial lung organoid for simulating a patient derived adenocarcinoma of lung for personalized oncology

Recent Advances in Alzheimer’s Disease Treatments with Therapeutic Antibodies to Amyloid-β

Tracing Alzheimer’s Genetic Footprints: A Pioneering Longitudinal Study Using Artificial Intelligence to Unravel Mutation- Driven Risks and Progression in Virtual Patients; Part 1 – The APOE genotypes

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