Department of Basic Medical Sciences, Faculty of Medicine, Galala University, Suez, Egypt.
Department of Physiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
J Physiol Sci. 2024 Sep 23;74(1):46. doi: 10.1186/s12576-024-00933-4.
Neurological disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD) have no disease-modifying treatments, resulting in a global dementia crisis that affects more than 50 million people. Amyloid-beta (Aβ), tau, and alpha-synuclein (α-Syn) are three crucial proteins that are involved in the pathogenesis of these age-related neurodegenerative diseases. Only a few approved AD medications have been used in the clinic up to this point, and their results are only partial symptomatic alleviation for AD patients and cannot stop the progression of AD. Immunotherapies have attracted considerable interest as they target certain protein strains and conformations as well as promote clearance. Immunotherapies also have the potential to be neuroprotective: as they limit synaptic damage and spread of neuroinflammation by neutralizing extracellular protein aggregates. Lately, disease-modifying therapies (DMTs) that can alter the pathophysiology that underlies AD with anti-Aβ monoclonal antibodies (MAbs) (e.g., aducanumab, lecanemab, gantenerumab, donanemab, solanezumab, crenezumab, tilavonemab). Similarly, in Parkinson's disease (PD), DMTs utilizing anti-αSyn (MAbs) (e.g., prasinezumab, cinpanemab,) are progressively being developed and evaluated in clinical trials. These therapies are based on the hypothesis that both AD and PD may involve systemic impairments in cell-dependent clearance mechanisms of amyloid-beta (Aβ) and alpha-synuclein (αSyn), respectively, meaning the body's overall inability to effectively remove Aβ and αSyn due to malfunctioning cellular mechanisms. In this review we will provide possible evidence behind the use of immunotherapy with MAbs in AD and PD and highlight the recent clinical development landscape of anti-Aβ (MAbs) and anti-αSyn (MAbs) from these clinical trials in order to better investigate the therapeutic possibilities and adverse effects of these anti-Aβ and anti-αSyn MAbs on AD and PD.
神经退行性疾病，如阿尔茨海默病（AD）和帕金森病（PD），目前尚无改变疾病进程的治疗方法，这导致了一场全球性的痴呆症危机，影响了超过 5000 万人。淀粉样蛋白-β（Aβ）、tau 和 α-突触核蛋白（α-Syn）是三种关键蛋白，它们与这些与年龄相关的神经退行性疾病的发病机制有关。到目前为止，临床上只使用了少数几种被批准用于 AD 的药物，它们的结果只是对 AD 患者的部分症状缓解，无法阻止 AD 的进展。免疫疗法引起了相当大的兴趣，因为它们针对特定的蛋白质株和构象，并促进清除。免疫疗法还有可能具有神经保护作用：通过中和细胞外蛋白质聚集体，限制突触损伤和神经炎症的传播。最近，基于可以用抗 Aβ 单克隆抗体（如 aducanumab、lecanemab、gantenerumab、donanemab、solanezumab、crenezumab、tilavonemab）改变 AD 病理生理学的疾病修饰疗法（DMTs）正在不断被开发和评估。同样，在帕金森病（PD）中，也在开发和评估利用抗 α-Syn（单克隆抗体）（如 prasinezumab、cinpanemab）的 DMTs。这些疗法基于以下假设：AD 和 PD 可能分别涉及细胞依赖的 Aβ 和 α-Syn 清除机制的全身性损伤，这意味着由于细胞机制故障，身体整体无法有效清除 Aβ 和 α-Syn。在这篇综述中，我们将提供使用 AD 和 PD 中单克隆抗体免疫疗法的可能依据，并强调这些临床试验中抗 Aβ（单克隆抗体）和抗 α-Syn（单克隆抗体）的最新临床开发情况，以便更好地研究这些抗 Aβ 和抗 α-Syn 单克隆抗体对 AD 和 PD 的治疗可能性和不良反应。
