Mivelsiran (ALN-APP) sodium is an siRNA targeting the β-amyloid precursor protein ( APP ). Mivelsiran sodium induces sequence-specific degradation of APP mRNA via RNA interference, thereby reducing the levels of APP protein and downstream amyloid cleavage products. Mivelsiran sodium reduces β-amyloid protein levels in the brain, alleviates neuroinflammation, and attenuates microglial proliferation. Mivelsiran sodium can be used for research on early-onset Alzheimer's disease [1].
In Vivo, Mivelsiran (0.07-0.9 mg; i.t.; single dose, monthly for 5 consecutive months) sodium induces dose-dependent, durable silencing of target gene expression across multiple CNS regions in male Sprague Dawley rats, with the 0.9 mg single dose reducing SOD1 mRNA to 25% of control levels and maintaining >50% silencing for over three months[1]. Mivelsiran (60-120 µg; i.c.v.; single dose) sodium suppresses APP expression, reduces neuroinflammation, and normalizes hyperactive behavior in cerebrovascular amyloid Nos2−/− (CVN) Alzheimer's disease mice[1]. Mivelsiran (300 µg; i.c.v.; two doses at 3 and 6 months, single dose at 8 months) sodium reduces amyloid beta levels, neuroinflammatory markers, and abnormal anxiety-like behavior in 5xFAD Alzheimer's disease mice when administered early, while late intervention does not improve behavioral deficits despite reducing pathological markers[1].
In Vitro, Mivelsiran sodium does not induce cytokine release or immune activation in ex vivo human whole blood[1].
References:
[1]. Titze-de-Almeida R, et al. C16-siRNAs in Focus: Development of ALN-APP, a Promising RNAi-Based Therapeutic for Alzheimer's Disease. Pharmaceuticals (Basel, Switzerland). 2025 Dec 22;19(1):26.
In Vivo, Mivelsiran (0.07-0.9 mg; i.t.; single dose, monthly for 5 consecutive months) sodium induces dose-dependent, durable silencing of target gene expression across multiple CNS regions in male Sprague Dawley rats, with the 0.9 mg single dose reducing SOD1 mRNA to 25% of control levels and maintaining >50% silencing for over three months[1]. Mivelsiran (60-120 µg; i.c.v.; single dose) sodium suppresses APP expression, reduces neuroinflammation, and normalizes hyperactive behavior in cerebrovascular amyloid Nos2−/− (CVN) Alzheimer's disease mice[1]. Mivelsiran (300 µg; i.c.v.; two doses at 3 and 6 months, single dose at 8 months) sodium reduces amyloid beta levels, neuroinflammatory markers, and abnormal anxiety-like behavior in 5xFAD Alzheimer's disease mice when administered early, while late intervention does not improve behavioral deficits despite reducing pathological markers[1].
In Vitro, Mivelsiran sodium does not induce cytokine release or immune activation in ex vivo human whole blood[1].
References:
[1]. Titze-de-Almeida R, et al. C16-siRNAs in Focus: Development of ALN-APP, a Promising RNAi-Based Therapeutic for Alzheimer's Disease. Pharmaceuticals (Basel, Switzerland). 2025 Dec 22;19(1):26.