Parkinson’s disease is characterized by the misfolding of certain proteins in human cells, which aggregate causing malfunction in the brain. Advantx‘s candidate ADV127 has been precisely designed to bind Sigma-1 receptors and activate key signaling pathways to restore protein folding homeostasis and stimulate neuronal regrowth.
This mitochondrial dysfunction causes the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies (LBs) compromising mitophagy, the process of eliminating damaged mitochondria, accelerating neurodegeneration. Simultaneously aggregation of α-Synuclein (α-Syn) and Tau protein and its interaction increases neurotoxicity, accelerates the loss of physiological function and axonal transport dysfunction, ultimately inducing the deposition of toxic fibrils and cell death.
The Sigma-1 receptor is a protein involved in the transport of lipids and proteins between cell organelles. Sigma-1 activation reduces the release of tumor necrosis factor α (TNF-α) responsible for α-Synuclein propagation, blocks tau hyperphosphorylation and aggregation, increases dopamine and dopaminergic fiber levels, promotes the elimination of damaged mitochondria, restores motor capacity, and also regulates the expression of proteins involved in neurite formation, synaptic plasticity, and presynaptic differentiation, suggesting that it could stimulate neuronal regrowth, axon extension, and recover cognitive deficits. In Parkinson’s disease, certain neuronal cells in the brain gradually break down or die mainly due to the dysfunction of their mitochondria, membrane-bound cellular organelles that generate most of the chemical energy needed to fuel the cell.
Potential market for Advantx candidate in Parkinson's disease
Prevalence>2.5m people in US/EU/UK/JP
Treated Population>2.1m patients
Market Growthest. 12.6% CAGR
data from Globaldata
Differentiated stages of Parkinson's disease
Parkinson’s disease is a genetically complex disorder, with multiple genes contributing to the risk of Parkinson’s disease and especially to the risk of developing Parkinson’s at a younger age. About 10 to 20 percent of people with Parkinson’s experience symptoms before age 50, which is called “young-onset.” Although the symptoms are the same, younger people may experience the disease differently and need treatments that provide cognitive recovery. Rarely, Parkinson’s-like symptoms can appear in children and adolescents. This form of the disorder is called juvenile parkinsonism and is often associated with specific high-risk genetic mutations for the disease.
LATE-ONSET AND DEMENTIA
Late-onset Parkinson’s disease, in addition to progressive motor symptoms such as slowness of movement, rigidity, tremors, and impaired balance, causes problems in cognitive function, such as forgetfulness, depression, paranoid thinking, sleep disturbances, and concentration problems. As the disease worsens over time, many people develop dementia. Parkinson’s disease dementia (PDD) is a common complication of Parkinson’s disease that severely affects patients’ health and quality of life. Nearly 70% of the Parkinson’s population has been diagnosed with dementia, and those with dementia have a lower survival rate compared to those without dementia.
ADV127 PD is Advantx’s candidate for the treatment of young and late-onset Parkinson’s disease and Parkinson’s Dementia.