Ladders to Cures Bets on 'Nodal Biology' to Make Rare Disease Drugs Profitable

Inside the Ladders to Cures Accelerator's Hunt for Shared Disease Mechanisms

Dr. Anna Greka, a Harvard professor and physician at Mass General Brigham, has spent her career looking for connections between diseases that most researchers treat as separate problems. At her lab, she oversees the Ladders to Cures Accelerator, an initiative at the Broad Institute designed to speed up the development of treatments for rare disease patients. The core idea is simple to state but hard to execute: find the biological points where different rare diseases converge, then build drugs that hit those shared targets.

Greka calls this approach "nodal biology." Instead of developing one drug for one rare disease — a market that may contain only a few thousand patients worldwide — her team looks for mechanisms that appear in several conditions at once. A single drug aimed at such a node could treat multiple diseases, dramatically expanding the number of patients it could serve. That larger patient population is what Greka argues makes the economics of rare disease drug development sustainable, because it gives companies a stronger commercial reason to invest.

The concept is not purely theoretical. In 2019, Greka and her team published a paper outlining a mechanism they discovered in a rare kidney disease that also plays a role in diseases affecting the eye and brain. With the accelerator, she hopes to uncover more of these nodal connections and move toward developing drugs that can treat them. On October 27, the Broad Institute will host the 3rd Annual Ladders to Cures Symposium, where Greka will appear alongside colleagues Dr. David Liu, Dr. Winston Yan and MIT economist Andrew Lo.

Why 'Nodal Biology' Could Rewrite Rare Disease Economics

The Economic Problem Nodal Biology Tries to Solve

Rare diseases are, individually, small markets. A condition affecting a few thousand people globally rarely justifies the hundreds of millions of dollars required to bring a new drug to approval. The result is a persistent funding gap: promising science stalls because the commercial case is too thin. Greka's nodal approach attacks that gap directly. If one drug can address several rare diseases through a shared mechanism, the addressable population multiplies, and the revenue potential rises accordingly. That, in her framing, is what makes the model economically sustainable rather than dependent on charity or one-off grants.

Where the Science Stands

The 2019 kidney disease paper is the proof point Greka cites. It showed that a mechanism underlying a rare kidney condition also operates in eye and brain diseases — evidence that nodal connections are real and discoverable, not just a hypothesis. The accelerator's task now is to industrialize that discovery process: systematically map where rare diseases overlap and then pursue drug candidates against those shared targets. That is a significant scientific undertaking, and the article does not specify how many nodal connections the team has identified or how far any drug program has advanced.

Who Is Positioned to Benefit

Pharma companies focused on rare disease — including Alexion, AstraZeneca's rare disease unit, which underwrites the CNBC Cures segment featuring this interview — have a direct interest in any model that widens patient populations and improves returns. For smaller biotechs, nodal drugs could offer a clearer path to partnerships or acquisition, since a multi-indication asset is easier to finance. For patients, the promise is faster access to treatments for conditions that have historically attracted little commercial attention. For context, the rare disease space has drawn growing pharma interest in recent years precisely because high prices and regulatory incentives can offset small populations — but that model has faced pricing pressure, which makes broader-population approaches like nodal biology more attractive.

What to Watch

The October 27 symposium is the next visible milestone, bringing together Greka's team, gene-editing researcher David Liu, Dr. Winston Yan and MIT economist Andrew Lo — a lineup that suggests the accelerator is thinking about both the science and the financing model. The key question is whether nodal biology can move from published mechanisms to actual drug candidates. Until that happens, the approach remains a promising framework rather than a proven commercial engine.

What the Nodal Approach Means for Pharma, Investors and Patients

The most important insight: nodal biology's real innovation is economic, not just scientific — it reframes rare disease drugs as multi-indication assets that can justify investment.

For pharma executives and investors watching the rare disease space, the Ladders to Cures model offers a template worth tracking. The 2019 kidney-eye-brain mechanism paper is the concrete evidence that shared targets exist; the accelerator's progress will show whether they can be found systematically.

• Watch the October 27 Ladders to Cures Symposium for signals on how many nodal connections the team has identified and whether any drug development programs have been launched.
• For business development teams at rare disease companies: multi-indication assets targeting shared mechanisms could become attractive licensing or acquisition targets, particularly if they address conditions that individually would not justify development costs.
• For investors: the presence of MIT economist Andrew Lo at the symposium suggests the accelerator is working on the financing architecture alongside the science — a detail worth following, since the model's viability depends on convincing capital that broader patient populations translate into reliable returns.
• For patient advocates: the approach could eventually widen the pipeline for conditions that have historically been overlooked, but no timelines for specific treatments have been announced.