What if we could tackle the
cause of Alzheimer’s and
Parkinson’s Disease?

Neurodegeneration

A hallmark of neurodegenerative diseases such as Alzheimer’s and Parkinson’s Disease, as well as rarer diseases such as Huntington’s Disease and Amyotrophic Lateral Sclerosis (ALS), is the appearance of cytotoxic, misfolded proteins. For example, it has long been known that the protein a-synuclein and the large aggregates of a-synuclein known as Lewy Bodies have been correlated with Parkinson’s Disease disease progression.

While functional a-synuclein is important for healthy brain function, excessive protein causes oligomers and aggregation, leading to neurotoxicity and the characteristic deadly symptoms of PD.

It’s likely that a-synuclein aggregation is caused by lysosomal misprocessing and that this dysfunction is in turn associated with dysfunctional autophagy

This hypothesis is underpinned by strong genetic evidence.

By restoring autophagy in such diseased cells we can remove the misfolded protein, such as a-synuclein, and restore lysosome function, something we have already demonstrated in cells derived from Parkinson’s DIsease patients and early onset Alzheimer’s patients.

iPS-derived GBA-mutated Parkinson’s Disease patient neurons exhibit reduced autophagy levels

Blue = DAPI (nuclei); Red = DQ-BSA (measure of lysosomal degradative activity)

The autophagy deficit in GBA patient neurons is rescued by TRPML1 activator SAM001

Parkinson’s Disease GBA patient neurons show increased α-synuclein aggregates

Green = aggregated a-synuclein (pS129 antibody)