Video:A mistake, a hunch—and a breakthrough

Sometimes you have to look in the wrong place to find the right answer.

Uche Medoh, MS ’22, PhD ’24, was a graduate student working in the lab of chemical engineer Monther Abu-Remaileh. Abu-Remaileh leads a research group that studies the inner workings of the recycling centers of our cells, small compartments called lysosomes that break down molecules once they are no longer needed. When the recycling centers fail, things can go terribly wrong.

Medoh had spent two years studying one such failure: Batten disease, an ultra-rare, progressive, and ultimately fatal neurological disorder. Patients, usually diagnosed at just a few years old, lose the ability to walk and talk, suffer from seizures, and live only into their teens or twenties. There is no cure. 

Scientists had already traced the disease to a single mutated gene. But what that gene did in healthy cells remained a mystery. Designing a treatment was like trying to fix a broken machine without knowing what it did in the first place.

Medoh was on the cusp of showing what the Batten’s gene was responsible for. But late one night, an experiment yielded an entirely unexpected result—one that would eventually lead to a stunning discovery. Until then, it had been widely believed that the lysosome merely breaks down particles, like a cell’s internal garbage disposal. Medoh now saw that the lysosome had the ability to make something new. 

He had stumbled onto something researchers studying Alzheimer’s and Parkinson’s were chasing for decades. The gene carries the instructions that cells need to produce an important molecule called bis(monoacylglycero)phosphate, or BMP. 

BMP is like the grease on the gears of the lysosome, according to Abu-Remaileh. With the right amount of BMP, the lysosome can properly churn through fatty molecules the cell no longer needs. Without it, those gears start to grind. Waste builds up. And in neurons, where there’s no room for error, that buildup turns deadly.

Scientists studying Alzheimer’s, Parkinson’s, and other more common neurodegenerative diseases had been looking for the elusive BMP-making machine for years. Why? Because changes in the amount of BMP in neurons is a hallmark of these diseases. But to make a medicine that could restore a normal amount of BMP, scientists needed to know what cellular machinery to target.

Medoh’s discovery changed that overnight. In trying to solve a rare disease, he revealed a missing link that might help treat far more common ones.

This is also where a lot of stories of scientific discovery end: publish the breakthrough, hope the right company sees its potential, and wait.

But Medoh and Abu-Remaileh did not want to wait. They teamed up with the Stanford Innovative Medicines Accelerator (IMA), itself a partnership between Sarafan ChEM-H and Stanford Medicine built to bridge the frustrating gap between academic discovery and drug development. By doing more of the early drug development work that universities typically are not equipped to do, the IMA boosts the transformative power of Stanford discoveries, helping researchers carry promising treatments further—and shortening the path from lab to patient bedside.

Abu-Remaileh’s team is working with industry-trained experts in the IMA, using sophisticated robotics and some chemical tricks to find a needle in the haystack. With support from the Knight Initiative for Brain Resilience, they are testing billions of molecules to find at least one that could restart BMP production and restore healthy recycling to the cell, slowing or stopping neurodegeneration. Once they identify a few promising leads, they will then work with drug designers to make them safer and more effective.

The road to a real medicine is long and winding, but the IMA is drawing new maps, helping scientists like Abu-Remaileh chart a course, and ensuring that the most promising discoveries have the best shot at changing the lives of patients and their families—not in the distant future, but as soon as possible.

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Abu-Remaileh is an assistant professor of chemical engineering and of genetics, and is a Sarafan ChEM-H Institute Scholar. Carolyn Bertozzi is the Baker Family Director of Sarafan ChEM-H, the Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences, and professor of chemistry.