Longitude Prize on ALS

Penn Medicine Against ALS: Stage 1 Discovery Award winner 

The Longitude Prize on ALS is one of the most coordinated bets the field has placed on curing ALS. It awards £100,000 to each of twenty Discovery Award teams worldwide, asking them to find new directions for ALS drugs that decades of research have missed. Yentli convened the team that submitted under the University of Pennsylvania, bringing together Penn faculty across multiple departments with PennMed Trainees Against ALS/FTD — a medical-student-led group whose work has been a vital component of the project — into one of those twenty teams.

Longitude Prize on ALS

The Penn team uses AI to find new drug targets for ALS by studying a family of proteins called RNA binding proteins. These proteins act like managers inside our cells, deciding which of our genes get used, when, and where. The system is so important that when it breaks down, the nerve cells that control movement die — and ALS begins. The most studied of these manager proteins is TDP-43, which is found in the wrong place and dysfunctional inside the cells of more than ninety-five percent of ALS patients and has been the central focus of ALS drug development for two decades. But TDP-43 does not work alone. Applied to one of the largest ALS patient datasets of its kind, the Penn team’s approach maps the whole network of proteins that work alongside TDP-43, surfacing drug-target candidates that a TDP-43-only search would miss.

For genetic ALS carriers — including Yentli, whose father died of C9orf72 ALS in 2024 — the search for a cure is not abstract. The Prize treats finding that cure as a portfolio problem: no single team is expected to solve ALS alone, but progress can come from any of the twenty, or from the combination. Stage 1 is the first step; subsequent stages carry larger funding for teams whose ideas hold up under more testing.

Yentli Soto Albrecht, MD-PhD student, C9orf72 genetic carrier, and Co-Founder of CureC9


Yentli Soto Albrecht

MD-PhD candidate, University of Pennsylvania

  • I am committed to finding a treatment for ALS before the disease takes me too — and the Longitude Prize on ALS has opened that door.

Yentli’s Message

The Penn Team


Faculty across multiple Penn departments, joined by PennMed Trainees Against ALS/FTD.

James Shorter, PhD  —  Project lead. Professor of Biochemistry and Biophysics, Penn Institute for RNA Innovation

Defne Amado, MD, PhD  —  Assistant Professor of Neurology, Perelman School of Medicine; Penn Comprehensive ALS Center

Corey T. McMillan, PhD  —  Associate Professor of Neurology; Penn Frontotemporal Degeneration Center; Penn BiND Lab

Edward B. Lee, MD, PhD  —  Professor of Pathology and Laboratory Medicine; Director, CNDR Brain Bank; Associate Director, Penn Alzheimer’s Disease Research Center

Michael Guo, MD, PhD  —  Assistant Professor, Perelman School of Medicine

Alessandra Chesi, PhD  —  Assistant Professor of Pathology and Laboratory Medicine

Ophir Shalem, PhD  —  Associate Professor of Genetics, Perelman School of Medicine and Children’s Hospital of Philadelphia

Yoseph Barash, PhD  —  Professor, Department of Computer and Information Science and Department of Genetics

César de la Fuente, PhD  —  Presidential Associate Professor, University of Pennsylvania

Yentli E. Soto Albrecht, PhD  —  MD-PhD candidate, Perelman School of Medicine; team convener

Scientists at UCLouvain — (sample provision & ALS expertise)

PennMed Trainees Against ALS/FTD  —  medical student led group; vital component of the project

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The Longitude Prize on ALS is an international research prize designed to speed up the discovery of new drugs for ALS. In Stage 1, twenty teams from around the world each received £100,000 to gather the first evidence that their idea for a new drug target is worth pursuing. Teams whose ideas hold up move on to later stages with larger amounts of funding. The Prize is built around the idea that no single team is likely to solve ALS alone — so it funds many strong teams in parallel and lets the best ideas advance.

Read me: https://als.longitudeprize.org/

RNA binding proteins are a large family of proteins that act like managers inside our cells. They decide which of our genes get used, when, and where — a system so important that when it breaks down, the nerve cells that control movement die and ALS begins.

TDP-43 is the best-known of these manager proteins in ALS. In the cells of more than ninety-five percent of ALS patients, TDP-43 ends up in the wrong place: clumping together in the body of the cell instead of staying in the nucleus where it does its job. For decades, finding ways to fix TDP-43 has been the central goal of ALS drug development.

But TDP-43 is only one of dozens of RNA binding proteins involved in ALS, and we are learning that the disease involves a much bigger network of these proteins working together. The Penn team is mapping that whole network — not just TDP-43 — to look for the most promising drug targets.

To go deeper on TDP-43, watch Episode 1 of Search for a Self Cure

Hospitals collect huge amounts of information about ALS patients — clinical notes, genetic data, scans, blood tests, and molecular profiles. There is far too much for any one person to look at all of it together. Modern AI can pick out patterns across all of those layers that no human reader could see by hand, and can suggest which biological pathways are most likely to lead to a useful drug. The Penn team applies these methods, an AI approach developed at Penn that is unpublished, to one of the largest ALS datasets of its kind, with the goal of producing a short list of the most promising targets to study next.

The Longitude Prize on ALS runs in stages. Stage 1 — called the Discovery Award — funds twenty teams worldwide at £100,000 each to do the first round of work: gathering the initial evidence that their proposed drug target is worth pursuing. Teams whose ideas hold up are eligible for later stages, which come with larger amounts of funding to take the work further. The Prize is structured so that the strongest targets — wherever they come from — can be supported all the way to a possible therapy.

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Several of these projects require funding, and the project needs for funds fluctuate. To donate to these efforts, please give to an unrestricted fund that is split evenly between End the Legacy and research projects driven towards curing genetic ALS/FTD.

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