AZTherapies Inc., Boston, MA, USA.
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129-2060, USA.
Sci Rep. 2021 Apr 13;11(1):8054. doi: 10.1038/s41598-021-85702-8.
Cromolyn is a known mast cell stabilizer and is approved for treatment of asthma and for other allergic indications. Cromolyn, in a new redesigned dry powder formulation, is being tested in a pivotal clinical trial in combination with low dose ibuprofen to treat early Alzheimer's Disease (AD) subjects. To better understand the mechanistic effect cromolyn has in slowing down or halting the neuroinflammatory response associated with AD progression, we tested the effect of cromolyn to dampen the inflammatory response in the human HMC3 microglia cell line. The direct effect of cromolyn on HMC3 microglia is on cytokines and chemokines production following their activation by the inflammatory cytokine TNF-α. Cromolyn and a new fluorinated analog dramatically reduced the secretion of a wide spectrum of inflammatory mediators, which included cytokines such as IL-1β, IL-6, IL-8 and IFN-γ, and chemokines such as CXCL10, CCL2, CCL3 and CCL4. These results bolster our understanding of how our cromolyn platform modulates toxic microglia behavior as a dynamic future treatment option for neurodegenerative disorders.
色甘酸钠是一种已知的肥大细胞稳定剂，已被批准用于治疗哮喘和其他过敏症。色甘酸钠的一种新的重新设计的干粉制剂正在进行一项关键性临床试验，与低剂量布洛芬联合用于治疗早期阿尔茨海默病（AD）患者。为了更好地了解色甘酸钠在减缓或阻止与 AD 进展相关的神经炎症反应方面的作用机制，我们测试了色甘酸钠对人 HMC3 小胶质细胞系炎症反应的抑制作用。色甘酸钠对 HMC3 小胶质细胞的直接作用是在炎症细胞因子 TNF-α激活后抑制细胞因子和趋化因子的产生。色甘酸钠和一种新型氟化类似物显著减少了广泛的炎症介质的分泌，其中包括细胞因子如 IL-1β、IL-6、IL-8 和 IFN-γ，以及趋化因子如 CXCL10、CCL2、CCL3 和 CCL4。这些结果支持了我们对我们的色甘酸钠平台如何调节毒性小胶质细胞行为的理解，作为神经退行性疾病的一种有前途的治疗选择。
