UCIBIO-Applied Molecular Biosciences Unit, School of Science and Technology, NOVA University of Lisbon, 2819-516 Caparica, Portugal.
Associate Laboratory i4HB-Institute for Health and Bioeconomy, School of Science and Technology, Nova University of Lisbon, 2829-516 Caparica, Portugal.
Int J Mol Sci. 2022 Aug 5;23(15):8725. doi: 10.3390/ijms23158725.
Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders' views on AI for therapy discovery in CDG.
研究进展推动了先天性糖基化障碍（CDG）的治疗发展，这是一组罕见的遗传疾病，影响蛋白质和脂质糖基化以及糖基磷脂酰肌醇锚生物合成。为新的医疗用途重新利用已知药物（称为药物再定位），无论是常见疾病还是罕见疾病，都越来越多。最新的创新涉及到合理寻找重新定位的分子，这也得益于人工智能（AI）。与传统方法相比，药物再定位加速了整个药物发现过程，同时节省了成本。这对于罕见疾病尤其有价值。人工智能工具已在罕见疾病的诊断、疾病分类和特征描述，以及最终的治疗发现方面证明了其价值。生物标志物和可靠疾病模型的可用性对于新药的研发至关重要，尤其是对于 CDG 等罕见且异质的疾病。这项工作综述了通过偶然发现或系统方法发现的用于 CDG 的重新定位药物的相关文献。还概述了生物标志物和疾病模型的最新进展，以及利益相关者对人工智能在 CDG 治疗发现中的看法。
