How Sanofi is Rewriting the Script for Untreated Rare Diseases

While the primary goal of Sanofi’s rare disease research is to develop treatments, the process delivers much more than just a therapy for a single condition. It deepens understanding of the underlying biology and advances the technologies that make future breakthroughs possible.

Researchers often look to the body’s own biology for inspiration when developing new therapies. One exciting example is how scientists are learning to piggyback on natural transport systems to deliver medicines into the brain, a place that researchers find notoriously hard to reach.

The blood-brain barrier is a protective layer that shields the brain from harmful substances in the bloodstream. But it also makes it difficult for most drugs to get through. Still, the brain has its own way of letting in essential nutrients—like iron or amino acids, which enter through specialized transporters.

At Sanofi, researchers are tapping into this very pathway. By engineering a therapeutic antibody to bind to one of these transporters, the body treats the medicine like a nutrient and carries it past the blood-brain barrier and into the brain. Once inside, the antibody can attach to its intended molecular target and directly trigger its therapeutic effect, opening the door to potential treatments for a wide range of rare neurological diseases. “And this is just the beginning. Sanofi researchers are expanding these strategies beyond the brain, exploring ways to deliver therapeutics to muscles and other specialized tissues,” Sardi says.

Another exciting example is the use of gene-editing technologies, where we want to harness precision tools to correct disease-causing mutations at their source. These advances, combined with innovations in delivery, are laying the foundation for treatments that were once unimaginable. For Sanofi, every breakthrough in rare diseases not only brings hope to patients but also builds a scientific toolbox—unlocking knowledge and technologies that will accelerate discoveries for years to come.

While all these advancements are exciting, no conversation about innovation would be complete without mentioning Artificial Intelligence (AI) and the profound ways it is transforming medical research. Its impact on rare disease research has been equally remarkable, opening up new possibilities that were previously out of reach.

One of the major applications of AI in rare disease research is improving how drugs are delivered to hard-to-reach organs like muscle and brain. Oftentimes, scientists use adeno-associated viruses (AAVs) as tiny delivery vehicles to carry healthy genes into the body. However, one of the biggest challenges has been getting these viruses to reach specific tissues like the muscle or brain, and to escape the body’s natural defense systems.

To overcome this, Sanofi researchers are actively exploring ways using AI to design better viral “shells,” called capsids. These engineered capsids can help the virus bypass immune responses and target precise cells with the goal of delivering therapies exactly where they are needed. Sanofi researchers are also using AI to connect vast datasets and uncover patterns that a human eye and brain couldn’t. They have recently published research on AI tools that have unlocked ways to spot mutations that, using a conventional way of screening, “would have taken decades to go through that number of mutations,” Sardi says. The use is coming equally fast in other areas including finding new drug targets, optimizing molecules, and generating novel hypotheses from complex data.

In rare diseases, many different genetic mutations might cause similar symptoms or disrupt similar biological functions. Now, researchers are looking at how AI is helping to bundle together different genetic signals that affect the same biological pathway and help unravel the common patterns between them. “If you look at them from a clinician perspective, there are different diseases, but they might have the same pathway affected,” he adds.

Unlike common diseases where researchers can use the same models trying to target different mechanisms, rare diseases research often requires its own specific animal model and dedicated research program. As a result, the effort and cost can multiply quickly even at the early research stage. That means, researchers often need a lot of resources up front to get to a first human trial. When it reaches patients for testing, these trials are also smaller and more focused and are designed around very specific patient groups. The bigger challenge there is usually around finding enough eligible patients to run the study.

Despite the technical and logistical challenges, Sardi’s passion for the field remains unshaken.

Another critical leap for the field will come from detecting disease much earlier in life. That’s why researchers are pushing for more advanced newborn screening programs. “Once you find the right molecules, you need to identify patients as soon as possible, as earlier treatments usually lead to better outcomes,” he adds.

“You could say we’re trying to play with nature—or even with what some might call God’s design,” Sardi adds. “Figuring out what is wrong and engineering a molecular solution that can fix it is just incredibly complex.”

Still, he says, “nature has given us these intricate biological mechanisms that sometimes go rogue. All we’re doing is trying to trick those systems into returning to a healthier state.”