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-syn 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 shown in cells derived from early onset Alzheimer’s patients.

Accumulation of enlarged lysosomes in untreated neurons.

Significant reduction in lysosome area after 24h treatment with
SAM19272 (left) and SAM7559 (right).

Accumulation of enlarged lysosomes in untreated neurons.

Significant reduction in lysosome area after 24h treatment with SAM19272 and SAM7559.

Samsara compounds reverse the pathological accumulation of late endosomes and lysosomes in neurons derived from a patient with early onset Alzheimer’s Disease.