Skylar-Scott Irina A, Sha Sharon J
Memory Disorders Division, Department of Neurology and Neurological Sciences, Stanford University School of Medicine, 213 Quarry Road, Palo Alto, CA, 94305, USA.
Curr Neurol Neurosci Rep. 2023 Oct;23(10):581-592. doi: 10.1007/s11910-023-01292-0. Epub 2023 Aug 12.
Lewy body dementia (LBD) encompasses dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). This article will emphasize potential disease-modifying therapies as well as investigative symptomatic treatments for non-motor symptoms including cognitive impairment and psychosis that can present a tremendous burden to patients with LBD and their caregivers.
We review 11 prospective disease-modifying therapies (DMT) including four with phase 2 data (neflamapimod, nilotinib, bosutinib, and E2027); four with some limited data in symptomatic populations including phase 1, open-label, registry, or cohort data (vodabatinib, ambroxol, clenbuterol, and terazosin); and three with phase 1 data in healthy populations (Anle138b, fosgonimeton, and CT1812). We also appraise four symptomatic therapies for cognitive impairment, but due to safety and efficacy concerns, only NYX-458 remains under active investigation. Of symptomatic therapies for psychosis recently investigated, pimavanserin shows promise in LBD, but studies of nelotanserin have been suspended. Although the discovery of novel symptomatic and disease-modifying therapeutics remains a significant challenge, recently published and upcoming trials signify promising strides toward that aim.
路易体痴呆（LBD）包括路易体痴呆（DLB）和帕金森病痴呆（PDD）。本文将重点介绍潜在的疾病修正疗法以及针对非运动症状（包括认知障碍和精神病）的研究性对症治疗，这些症状会给LBD患者及其护理人员带来巨大负担。
我们回顾了11种前瞻性疾病修正疗法（DMT），其中4种有2期数据（奈非那明、尼洛替尼、博舒替尼和E2027）；4种在症状性人群中有一些有限数据，包括1期、开放标签、登记或队列数据（沃达巴替尼、氨溴索、克伦特罗和特拉唑嗪）；3种在健康人群中有1期数据（Anle138b、福斯戈尼美顿和CT1812）。我们还评估了4种针对认知障碍的对症疗法，但由于安全性和有效性问题，只有NYX-458仍在积极研究中。在最近研究的精神病对症疗法中，匹莫范色林在LBD中显示出前景，但奈洛坦色林的研究已暂停。尽管发现新的对症和疾病修正疗法仍然是一项重大挑战，但最近发表的和即将进行 的试验表明朝着该目标迈出了有希望的步伐。
