Chatterjee Receives Donation to Study Fatal Neurological Disease

Michaela Martinez

3/12/24 Pratt School of Engineering

Pranam Chatterjee will explore how to degrade a key protein that causes Alexander Disease

Chatterjee Lab — Chatterjee Receives Donation to Study Fatal Neurological Disease

Pranam Chatterjee, assistant professor of biomedical engineering at Duke University, received a donation of $50,000 from the foundation EndAxD.

A nonprofit dedicated to the research, treatment, and discovery of a cure for Alexander Disease, EndAxD’s goal is to help patients get the appropriate care.

Alexander disease is an extremely rare genetic disease that affects one out of a million patients every year and is caused by mutations in the gene GFAP. This gene is responsible for providing structure and strength to glial cells, which in turn help modulate and support neuronal signaling pathways.

In healthy nervous systems, nerves are coated in a fatty layer of myelin, which helps insulate the nerves in the brain and spinal cord and promotes the rapid transmission of nerve signals, allowing the nervous system to properly function.

But in Alexander disease, mutations in the GFAP protein cause this myelin sheath to degrade, leading to a multitude of problems ranging from developmental delays to seizures. The disease is most commonly diagnosed in early childhood, and there is currently no cure.

With the support from EndAxD, Chatterjee plans to develop a platform that can target and degrade the mutated GFAP. Working at the intersection of generative artificial intelligence (AI) and experimental bioengineering, Chatterjee and his team have recently developed AI algorithms that can design binding peptides to previously undruggable target proteins.

For example, his lab’s most recent algorithm, PepMLM, generates binding peptides that can precisely and accurately bind using only a small target protein sequence. This work has allowed them to create new therapeutic tools, called “ubiquibodies,” that can bind to and degrade these target proteins.

Our goal for the first year of the project is to identify, design and optimize ubiquibodies that can specifically and efficiently degrade GFAP proteins. It’s a hard protein to target, so if we can prove that our approach will work, that would be a significant step forward. GFAP proteins are a potential target in a lot of neurodegenerative diseases, so there is a lot of motivation for us to figure out how we can break it down.
Pranam Chatterjee Assistant Professor of Biomedical Engineering

Chatterjee and his team are looking forward to using their unique combination of computational and wet-lab tools to develop potential new therapies for this devastating disease.

“Not only is EndAxD giving us financial support to study Alexander disease, but they are also giving us access to specific cell lines, animal models and a community of researchers that will help us go after this disease,” said Chatterjee. “I’m grateful to EndAxD for providing us with the support to take this on.”

“We are grateful to Duke University, Dr. Chatterjee, and his team for the opportunity to partner on this groundbreaking research” said Laura Ledbetter, co-founder of End AxD. “ Our hope is this investment will bring us closer to a treatment and eventual cure of Alexander disease”.