All Research

Large-scale drug screening in iPSC-derived motor neurons from sporadic ALS patients identifies a potential combinatorial therapy

Read the paperDOI: 10.1038/s41593-025-02118-7

TL;DR

Imagine if scientists could take a small sample of your skin, turn those cells into the exact type of brain cells that are dying in ALS, and then test hundreds of potential medicines on them in a lab dish. That's essentially what this research accomplished. Scientists took skin cells from 100 people with ALS, converted them into motor neurons (the brain cells that control muscle movement), and discovered that these lab-grown neurons died in the same way as they do in actual ALS patients. When they tested over 100 drugs that had failed in human trials, 97% also failed in their lab model - proving their system works like the real disease. Most importantly, they found a combination of three drugs that kept the neurons alive longer, offering new hope for treatment.

Heterogeneous and predominantly sporadic neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), remain highly challenging to model. Patient-derived induced pluripotent stem cell (iPSC) technologies offer great promise for these diseases; however, large-scale studies demonstrating accelerated neurodegeneration in patients with sporadic disease are limited. Here we generated an iPSC library from 100 patients with sporadic ALS (SALS) and conducted population-wide phenotypic screening. Motor neurons derived from patients with SALS recapitulated key aspects of the disease, including reduced survival, accelerated neurite degeneration correlating with donor survival, transcriptional dysregulation and pharmacological rescue by riluzole. Screening of drugs previously tested in ALS clinical trials revealed that 97% failed to mitigate neurodegeneration, reflecting trial outcomes and validating the SALS model. Combinatorial testing of effective drugs identified baricitinib, memantine and riluzole as a promising therapeutic combination for SALS. These findings demonstrate that patient-derived iPSC models can recapitulate sporadic disease features, paving the way for a new generation of disease modeling and therapeutic discovery in ALS.

  • 1Generated an iPSC library from 100 patients with sporadic ALS and demonstrated that motor neurons derived from these patients showed reduced survival and accelerated neurite degeneration compared to controls
  • 2Screening of over 100 drugs previously tested in ALS clinical trials revealed that 97% failed to mitigate neurodegeneration in the SALS model, reflecting real clinical trial outcomes
  • 3Identified a promising therapeutic combination of baricitinib, memantine and riluzole that significantly increased survival of SALS motor neurons
  • 4Demonstrated that SALS motor neurons exhibited transcriptional dysregulation consistent with postmortem spinal cord tissues from ALS patients and showed pharmacological rescue by riluzole
  • 5Established the first validated model of sporadic ALS using patient-derived iPSCs that recapitulates key disease features and correlates with donor survival
Nature·

Over 20,000 precolonial earthworks in the Southwest Amazonia

Imagine flying a special laser scanner over the Amazon jungle that can 'see through' the treetops, like X-ray vision for the ground. When scientists did this, they found over 20,000 geometric shapes — ditches, mounds, and enclosures — built by ancient people long before Europeans arrived. These aren't small things: they're massive earthen structures, like monuments. This means the Amazon rainforest, which most people picture as empty wilderness, was actually home to millions of people who built cities and shaped the landscape. Think of it like discovering that a forest you thought was wild was actually someone's ancient garden on a continental scale.

Nature·

A digitally controlled silicon quantum processing unit

Imagine you want to build a super-powerful calculator that uses the weird rules of quantum physics to solve problems no regular computer can. The trouble is, the tiny quantum pieces — called qubits — are incredibly fragile and need to be kept colder than outer space. On top of that, you need wires and control signals going to every single qubit, and if you have thousands of them, the wiring becomes a nightmare. This team solved part of that puzzle by building their qubits out of silicon (the same stuff in your phone's chip), adding a tiny control computer that works at super-cold temperatures right next to the qubits, and using a special high-density cable to connect everything cleanly. They packed 54 tiny quantum dots onto a chip, arranged 18 of them into working qubits, and showed the qubits work about 10 times better than any previous silicon qubit of this type. They also ran basic error-correction experiments to prove the system is on track for real-world use.

Scientific American·

The 2026 World Cup's grass is an engineering problem

Imagine you're trying to play soccer in 16 different places across the United States, Canada, and Mexico — some in freezing cold, some blazing hot, some in stadiums with roofs that block sunlight. Half of those stadiums normally use fake grass. Now FIFA, the organization that runs the World Cup, wants every single pitch to feel and play exactly the same way, like a video game where every level has identical physics. To do that, they hired grass scientists — yes, that's a real job — who figured out how to grow special grass on thin mats with plastic underneath so it can be transported like a carpet, stitched with synthetic fibers so it doesn't rip when players sprint and tackle, and tested by literally shooting balls at it with a cannon to make sure it bounces right. Different grass species are used depending on whether a stadium is hot, cool, or dark. It's basically a giant, living, high-tech floor installation that has to survive the world's best athletes running on it.

Monthly Notices of the Royal Astronomical Society·

Remarks on the disproof of the unit distance conjecture

Imagine you scatter a bunch of dots on a piece of paper. The question is: how many pairs of those dots can be exactly 1 inch apart? The Erdős unit distance conjecture asked whether there's a specific mathematical formula that limits how often this can happen as you add more and more dots. Think of it like asking how many friendships can exist in a town where friends are defined as people who live exactly one mile apart — there's a suspected maximum, and Erdős guessed what that maximum should be. For decades, no one could prove or disprove his guess. Now, an AI apparently found a specific arrangement of dots (a 'counterexample') that breaks the expected limit, proving Erdős's conjecture was wrong. A team of elite mathematicians then checked and explained the AI's work in this paper.