The hallmark of Parkinson's is the degeneration of neurons in the brain, which results in motor dysfunction, behavioural changes, and in some cases dementia. The pathology of Parkinson’s disease shares a lot of similarities with Alzheimer’s, more specifically, both are characterised by the misfolding and aggregation of proteins, which triggers the formation of amyloid fibrils. These fibrils accumulate in structures such as Lewy bodies and neurofibrillary tangles, contributing to the deterioration of neural function.
PET imaging shows that accumulation of aggregated proteins can begin up to 20 years before clinical symptoms onset. In Alzheimer’s disease, there is a very specific in vitro diagnostics where scientists can quantify the aggregates or markers of the aggregates in CSF and blood. While for Parkinson’s, there are no synuclein markers or biomarkers from an imaging point of view.
Dr. Gergely Toth, Chief Executive and Chief Scientific Officer of Cantabio Pharmaceuticals, presented on the development of precision therapeutics for Parkinson’s disease. His work centres around the DJ-1 protein.
DJ-1 is a promising therapeutic target for Parkinson’s disease due to its genetic links, functional versatility, and role in mitigating oxidative and aggregation-related damage. Cantabio’s precision therapeutic platform aims to develop disease-modifying treatments by capitalising on DJ-1 biology.
Dr Toth added that oxidative stress and protein aggregation (especially of alpha-synuclein and tau) are central to Parkinson's pathology. DJ-1 oxidation is a key contributor to neuronal damage in Parkinson’s. Furthermore, DJ-1 is also implicated in mitochondrial dysfunction.
Mutations in DJ-1 are linked to early-onset familial Parkinson’s disease, and even in idiopathic cases, DJ-1 seems to play a significant role. Toth’s research has shown that DJ-1 aggregates in Parkinson’s brains and co-localises with markers of α-synuclein and Tau, suggesting its involvement in disease pathology. Importantly, the oxidised form of DJ-1 interacts with α-synuclein and inhibits its aggregation. This indicates a protective mechanism.
Cantabio Pharmaceuticals has developed a biomarker platform to quantify oxidised and unoxidised DJ-1 in tissues and biofluids, which could assist with diagnosis and patient stratification.
Dr Toth is exploring therapeutic strategies, including small molecule pharmacological chaperones, such as CB-125, which stabilise DJ-1 and show efficacy in cell and animal models. Another method involves a cell-entering version of DJ-1 that can enter cells and the brain. Toth claimed that this demonstrated protective effects against oxidative and glyoxal stress and inhibited α-synuclein aggregation.
The early detection of protein aggregation opens options for pre-symptomatic intervention. This mission aligns with Cantabio’s goal: to develop disease-modifying therapies that treat the root causes rather than just symptoms.
