What if we could detect and repair the earliest stages of protein dysfunction to eliminate neurodegenerative disease?

The Problem

• Proteins are tiny machines in our cells that need to fold into the right shape to work. Sometimes they get the wrong signals and fold the wrong way or stick together, forming clumps (aggregates) that damage cells. This damage can lead to Alzheimer’s disease, ALS, some cancers, and other chronic and degenerative conditions. 
• Getting older, having certain genes, or being exposed to toxins can all cause proteins to misfold. 
• We don’t have good tools to predict, stop, or undo these early misfolding and clumping events. 
• Most treatments go after large protein clumps that show up late in disease, when much of the damage is already done. At that point, it is very hard to get cells working normally again. Many of the proteins involved are very flexible and hard for current drugs to target, so they are often called “undruggable.” 

The Solution

• BIOGAMI focuses on the very earliest steps in the misfolding process, especially in the brain and other vulnerable tissues. 
• The program will decode the “grammar” that guides how flexible, disordered proteins behave and create new ways to steer misfolded or clumped proteins back into healthy shapes. 
• BIOGAMI will build tools to detect the earliest warning signs of protein misfolding and clumping. 
• By acting this early, BIOGAMI aims to stop neurodegenerative and other chronic diseases before they fully develop, instead of only treating symptoms after serious damage has occurred. 

Only ARPA-H can...

• break down research silos working to understand these flexible, disordered proteins, 
• bring together experts in protein science, AI, and computing to rewrite this molecular grammar, and 
• accelerate progress in the long fight against neurodegenerative diseases and chronic illnesses.