AI-Designed 'Intrabodies' Could Open New Paths to Treating Alzheimer's, Parkinson's and MND

Researchers at the University of Essex, working with an international team, have used artificial intelligence to redesign small antibody fragments so they can function inside human cells rather than outside them, where antibodies normally work. The engineered fragments, called intrabodies, are built to attach to proteins linked to neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's and motor neurone disease (MND). The work, funded by the MND Association, was published in Nature Communications.

Led by Dr. Caitlin O'Shea and Dr. Gareth Wright of the School of Life Sciences, the team found that electrical charge is a key factor in whether an antibody fragment can remain stable inside a cell instead of clumping together. "Antibodies usually have the wrong charge to exist inside cells without sticking together," O'Shea said. Using software developed by Nobel laureate David Baker's group, the researchers redesigned the fragments to carry the right charge, converting 672 different antibodies into stable intrabodies.

Wright said the redesigned molecules stick to proteins that cause neurodegenerative diseases affecting over one million people in the UK alone, conditions that currently have no cures. The team plans to make the redesigned molecules freely available to other scientists, potentially letting researchers repurpose millions of existing antibodies developed over decades of biomedical research as laboratory tools or future treatment candidates.

Dr. Brian Dickie, Chief Scientist at the MND Association, called the work "a significant advance in overcoming one of the key challenges that has impeded the development of antibodies as treatments" for diseases like MND, adding that combining intrabody science with emerging gene therapy techniques "may lead to new therapeutic strategies that can hit specific molecular targets within neurones."