Unlocking the Brain's Secrets: How Aerska's RNAi 'Shuttles' Could Revolutionize Neurodegenerative Disease Treatment

A group of RNA veterans is launching a new startup aimed at getting RNA-interfering (RNAi) molecules into the brain to silence the genes that cause neurodegenerative diseases. Called Aerska, the Dublin-headquartered firm has raised $21 million in seed funding, with plans to treat Alzheimer’s and Parkinson’s diseases.

"It started in a pub in Ireland, like all good ideas," says CEO Jack O’Meara. It was late 2024, and O’Meara had just stepped away from Ochre Bio, a startup he’d cofounded to make RNAi drugs to treat liver diseases. O’Meara had for years wanted to use RNAi to tackle brain disorders, but he’d run into a series of technical challenges: first, getting RNAi molecules across the blood-brain barrier, then getting them to distribute throughout the brain’s 400 miles of capillaries instead of settling in one spot.

Meetings in bars and restaurants in Ireland and Boston sparked the beginnings of Aerska. O’Meara reconnected with Stuart Milstein, a former Alnylam Pharmaceuticals scientist who’d helped lead neuroscience efforts at the RNAi-focused firm, and David Coughlan, another Ochre Bio veteran, to help refine his ideas. O’Meara then reached out to some of his former investors. It didn’t take long for Aerska to get off the ground: the startup emerged from stealth on Wednesday with 15 employees spread across Ireland, the UK, and the US, including Milstein as cofounder and Coughlan as head of early development.

Aerska’s key technology is what O’Meara and his team have termed "brain shuttles".

The blood-brain barrier strictly controls what molecules can pass into the brain, and the endothelial cells that make up the barrier have receptors that determine which molecules, like iron and glucose, they can safely allow across the wall. "We basically try and trick the blood-brain barrier into thinking your RNA is something it wants to internalize," O’Meara says.

To do that, the Aerska team attaches transferrin-receptor-targeting antibodies to the interfering RNA molecules, making antibody-oligonucleotide conjugates. The shuttle binds to that receptor, "and then the payload gets pulled across [the blood-brain barrier], in concert with the antibody or peptide that’s used to conjugate the RNA." From there, the RNAi medicine would—in theory—be distributed throughout the brain through its bloodstream.

O’Meara and his team are hoping to avoid spinal injections and intravenous infusions, instead engineering for a more patient-friendly approach: under-the-skin injections, the same way medicines like semaglutide are administered. But that’s still a few years away. O’Meara says Aerska is in conversation with potential licensing partners for technology that could speed up the startup’s preclinical work. The $21 million seed round will last a couple of years. After that, O’Meara will need to raise more money before Aerska can begin testing in humans.

O’Meara and his team intend to take a precision medicine approach to treating Alzheimer’s and Parkinson’s diseases. That is, they will likely try to find certain subpopulations that have a greater chance of responding to Aerska’s drug candidates.

"We’re looking for patient populations where we’re more confident in the biology and the target that we’re going for," O’Meara says. "If we could try to take some lessons learned from the oncology field, once you start to divide these diseases up into more tractable subdiseases, they get easier."