Researchers at the University of Essex have developed microscopic drugs that could pave the way for new approaches to treating neurodegenerative diseases such as Alzheimer’s, Parkinson’s and motor neurone disease (MND).
Working with an international team, scientists used artificial intelligence to create extremely small antibody fragments that can be produced directly within human cells. Once there, the fragments can attach to proteins associated with diseases.
Ordinary antibodies generally work outside of cells. Instead, the newly redesigned fragments, called intrabodies, have been designed to remain stable within cells, allowing them to target proteins involved in neurodegenerative conditions.
Electrical charge helps antibodies survive inside cells
The research was funded by the MND Partnership and led by Dr Caitlin O’Shea and Dr Gareth Wright from the Faculty of Life Sciences. The team discovered that electrical charge is a key factor in determining whether antibody fragments can remain stable and functional within cells.
Using that information along with AI-powered protein redesign, the researchers converted 672 different antibodies into intrabodies capable of targeting important disease-related proteins.
The breakthrough could give scientists new ways to study and potentially treat neurodegenerative diseases by acting directly inside living cells, where many of the biological processes involved in these conditions begin.
After the publication of the research in Nature CommunicationsThe redesigned molecules will be freely available to other scientists.
Lead author Dr O’Shea, who specializes in MND and Parkinson’s disease, said: “We looked at the properties of millions of antibodies and compared them to human proteins found inside the cell.
“From this we discovered that antibodies normally have the wrong charge to exist inside cells without sticking together.
“We used software developed by Nobel Prize winner David Baker and his group to redesign our antibody fragments so they had the right charge and were super stable.”
Repurposing millions of existing antibodies
The researchers believe the findings could allow scientists to find new uses for millions of antibodies developed over decades of biomedical research.
Rather than starting completely from scratch, existing antibodies can be adapted for use as powerful laboratory tools and, potentially, as a basis for future treatments targeting disease-causing proteins.
Dr Wright, who led the research, said the approach could have important implications for diseases that affect tens of millions of people around the world.
“We have created intracellular antibodies that attach to proteins that cause neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and motor neuron disease,” Dr. Wright said.
“These diseases can cause cognitive impairment, forgetfulness, loss of muscle control and death. They affect more than a million people in the UK alone, making them a major public health problem.
“There are no cures for these diseases and finding molecules that interact with the proteins that cause them in their native environment is a major challenge in the drug discovery process.”
New therapeutic possibilities for MND and other diseases
The MND Association welcomed the findings and highlighted their potential importance for future treatments.
The charity’s chief scientist, Dr Brian Dickie, said: “Dr Wright and his colleagues have made significant progress in overcoming one of the key challenges that has prevented the development of antibodies as treatments for neurodegenerative diseases, such as MND.
“Their research findings provide optimism that a combination of this new ‘intrabody’ science with emerging gene therapy techniques may lead to new therapeutic strategies that can hit specific molecular targets within neurons.”