PIPELINE

Modify disease with microbiome-derived small molecules

Our lead candidate, STL-101, is a potential first-in-class, disease-modifying therapy for Parkinson’s disease that acts through neuroprotection.

Regulate proteins to regulate disease

STL-101 is a synthetic form of queuine, a micronutrient made by gut bacteria.

 

Queuine is enriched in the central nervous system and crosses the blood-brain barrier.

STL-101 is a synthetic form of queuine, a metabolite made exclusively by bacteria. Once produced in our gut, queuine is absorbed through the digestive tract and travels throughout the body. It is integrated into transfer RNA (tRNA) at the ‘wobble position’ and improves the speed and fidelity of mRNA translation. Queuine, being a naturally occurring nucleobase, has a de-risked safety profile at physiologically relevant concentrations.

Regulate proteins to regulate disease

STL-101 is a synthetic form of queuine, a micronutrient made by gut bacteria.

Queuine is enriched in the central nervous system and crosses the blood-brain barrier.

hhh

Q-tRNA improves the fidelity of mRNA translation and prevents protein misfolding / aggregation [1,2,3,4]

1- Zaborske et al., PLoS Biology, 2014

2- Tuorto et al., EMBO J, 2018

3- Müller et al., NAR, 2019

4- Suzuki et al., Nat Comm, 2020

Queuine is enriched in the central nervous system

Less queuine = less dopamine

In Parkinson’s disease, allowing the insertion of queuine in tRNA may lead to more BH4, which is needed to create dopamine

STL-101
protects neurons from cell death

STL-101 protects primary dopaminergic neuronal cultures against neurotoxin-induced cell death

STL-101 protects from toxic protein aggregation

STL-101 prevents the aggregation of alpha-synuclein which is associated with the degeneration of dopaminergic neurons

For further information see
“ Queuine, a bacterial derived hypermodified nucleobase, shows protection in in vitro models of neurodegeneration ” on BioRXiv