ADV127-PD for Parkinson’s Disease:

  • Best-in-class Sigma1 agonist
  • High Potency​
  • Higher Selectivity​
  • Unambiguous activity
  • Oral monotherapy
  • Pharmaceutical profile​
  • Low potential for clinical drug-drug interactions

Mechanism of Action on Parkinson’s Disease

ADV127 candidate has been designed to exert a disease-modifying, neuroprotective effect, in Parkinson’s Disease by downregulating cellular stress and eliciting pro-survival and anti-apoptotic signaling, paralleled by an increased density of dopaminergic fibers in denervated striatal regions, and recovering of dopamine levels.
Activation of Sigma-1 receptors decreases astrogliosis and upregulates neurotrophic factors (BDNF and GDNF) and their downstream effector pathways, also leading to increased neurotrophin secretion, enhancing neurotrophin receptor-mediated neurite outgrowth through activation of tropomyosin receptor kinase (Trk). Sigma-1 receptor activation and subsequent interaction with IP3 receptors may also mediate pharmacological effects on neurite outgrowth. Sigma-1 activation also inhibits M1 microglial polarization and promotes M2 polarization, reducing the release of anti-inflammatory cytokines (IL-10) and inducible nitric oxide synthase (iNOS), produced by the accumulation of α-synuclein. Notably, activation of Sigma-1 reduces the production of proinflammatory mediators, TNF-α, and IL-1β. TNF-α induces neuronal senescence and enhances the senescence-associated secretory phenotype (SASP) of neurons and subsequent lysosome-dependent secretion of α-synuclein aggregates, resulting in increased cell-to-cell propagation of α-synuclein, thought to be the underlying mechanism of Parkinson’s disease progression.
Learn more

Chung, C.G., Lee, H. & Lee, S.B. Mechanisms of protein toxicity in neurodegenerative diseases. Cell. Mol. Life Sci. 75, 3159–3180 (2018).​

In-vivo preclinical validation in progress.

  • AAV-A53Tg rat model of Parkinson’s disease
    • Cylinder Test: ADV127 demonstrated a significant improvement in motor behavior.