Hurvitz Noa, Dinur Tama, Revel-Vilk Shoshana, Agus Samuel, Berg Marc, Zimran Ari, Ilan Yaron
Departments of Medicine and Neurology, Hadassah Medical Center, Jerusalem 9112001, Israel.
Gaucher Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
J Clin Med. 2024 Jun 5;13(11):3325. doi: 10.3390/jcm13113325.
Gaucher Disease type 1 (GD1) is a recessively inherited lysosomal storage disorder caused by a deficiency in the enzyme β-glucocerebrosidase. Enzyme replacement therapy (ERT) has become the standard of care for patients with GD. However, over 10% of patients experience an incomplete response or partial loss of response to ERT, necessitating the exploration of alternative approaches to enhance treatment outcomes. The present feasibility study aimed to determine the feasibility of using a second-generation artificial intelligence (AI) system that introduces variability into dosing regimens for ERT to improve the response to treatment and potentially overcome the partial loss of response to the enzyme. This was an open-label, prospective, single-center proof-of-concept study. Five patients with GD1 who received ERT were enrolled. The study used the Altus Care™ cellular-phone-based application, which incorporated an algorithm-based approach to offer random dosing regimens within a pre-defined range set by the physician. The app enabled personalized therapeutic regimens with variations in dosages and administration times. The second-generation AI-based personalized regimen was associated with stable responses to ERT in patients with GD1. The SF-36 quality of life scores improved in one patient, and the sense of change in health improved in two; platelet levels increased in two patients, and hemoglobin remained stable. The system demonstrated a high engagement rate among patients and caregivers, showing compliance with the treatment regimen. This feasibility study highlights the potential of using variability-based regimens to enhance ERT effectiveness in GD and calls for further and longer trials to validate these findings.
1型戈谢病（GD1）是一种隐性遗传的溶酶体贮积症，由β-葡萄糖脑苷脂酶缺乏引起。酶替代疗法（ERT）已成为GD患者的标准治疗方法。然而，超过10%的患者对ERT反应不完全或部分丧失反应，因此需要探索替代方法来提高治疗效果。本可行性研究旨在确定使用第二代人工智能（AI）系统的可行性，该系统在ERT给药方案中引入变异性，以改善治疗反应并可能克服对酶的部分反应丧失。这是一项开放标签、前瞻性、单中心概念验证研究。招募了5名接受ERT的GD1患者。该研究使用了基于手机的Altus Care™应用程序，该程序采用基于算法的方法，在医生设定的预定义范围内提供随机给药方案。该应用程序能够实现个性化治疗方案，剂量和给药时间有所变化。基于第二代人工智能的个性化方案与GD1患者对ERT的稳定反应相关。一名患者的SF-36生活质量评分有所改善，两名患者的健康变化感有所改善；两名患者的血小板水平升高，血红蛋白保持稳定。该系统在患者和护理人员中显示出较高的参与率，表明他们遵守治疗方案。这项可行性研究突出了使用基于变异性的方案来提高ERT在GD中的有效性的潜力，并呼吁进行进一步和更长时间的试验来验证这些发现。
