Targeting the biology behind ALS
Project Saguaro is leveraging advances in RNA biology to urgently develop new medicines targeting ALS and frontotemporal dementia.
May is ALS Awareness Month — a moment to recognize how much is at stake for patients with amyotrophic lateral sclerosis, a progressive and fatal neurodegenerative disease with no effective treatments. For the more than 30,000 Americans living with ALS, and the families beside them, that need is real and immediate.
At Sanford Labs, that urgency is built into how we work. Our mission is to advance RNA biology toward new medicines — moving programs from early science through key milestones and then partnering with biopharma to carry them into patients. Project Saguaro, targeting ALS and frontotemporal dementia, reflects that mission in action.
The biology we’re targeting
A key feature of ALS — and the related neurodegenerative disease frontotemporal dementia (FTD) — is the dysfunction of TDP-43, an RNA-binding protein that normally resides in the nucleus. In affected neurons, TDP-43 mislocalizes to the cytoplasm, where it forms toxic aggregates. The result is a dual problem: the nucleus loses a protein it needs to function, while the cell accumulates inclusions it struggles to clear. This combination drives neuronal cell death and has proven difficult to address with conventional therapeutic approaches.
Our approach
Project Saguaro is focused on developing a treatment that addresses both dimensions of TDP-43 dysfunction — preventing or reversing cytoplasmic aggregation and restoring normal nuclear function. We are pursuing two parallel drug strategies, an antisense oligonucleotide approach and a small molecule approach, each targeting a specific cellular protein that is required for TDP-43 to be recruited into cytoplasmic aggregates. As Sebastian Markmiller, PhD, Group Leader for Project Saguaro, explains: “Most ALS treatments focus on symptoms or only help a small subset of patients. Our approach aims to go deeper, targeting the disease itself with the potential to help many more people living with ALS.”
The program is currently advancing toward partnership — a signal of both the scientific progress and the broader opportunity we see in this space.
Why RNA therapeutics
RNA therapeutics offers tools that conventional drugs simply don’t have — the ability to intervene precisely at the level of gene expression, to modulate proteins that have been considered undruggable, and to address the root biology of disease rather than its downstream effects. For a problem like TDP-43 dysfunction, that precision matters. As President and CEO Kristiina Vuori notes: “Sanford Labs was built to translate breakthroughs in RNA biology into transformative therapies. That’s exactly why ALS is such an important focus for us: by precisely restoring the function of TDP-43, we have the potential to address a core driver of disease in ways conventional approaches cannot.”
Looking ahead
Project Saguaro is one of several programs we’re advancing across RNA therapeutics — each targeting a different aspect of RNA biology, and collectively aimed at diseases with pressing unmet medical needs. For a more complete look at our research portfolio, watch for our refreshed website launching this summer.