Microscopic medicines unlock new treatments for MND and Alzheimer’s
New treatments for neurodegenerative diseases like Alzheimer’s, Parkinson’s, and motor neurone disease (MND) could be unlocked thanks to microscopic medicines developed by researchers at the University of Essex.
Using artificial intelligence, an international team of scientists has created tiny antibody fragments that can be made directly inside human cells, where they bind to proteins linked to disease.
Normally, antibodies can only function outside cells.
But these redesigned fragments, known as intrabodies, are engineered to survive inside cells and target the proteins that drive neurodegenerative conditions.
The MND Association-funded research, led by Dr Caitlin O’Shea and Dr Gareth Wright from the School of Life Sciences, found that electrical charge plays a crucial role in whether these antibody fragments remain stable and usable inside cells.
By combining that knowledge with AI-based protein redesign, the researchers were able to convert 672 different antibodies into intrabodies that target key disease-related proteins.
The work could help researchers develop new tools and therapies that act directly inside living cells, where many neurodegenerative diseases begin.
These redesigned molecules will be made freely available to other scientists now the research has been published in Nature Communications.
Lead author Dr O’Shea, who specialises in MND and Parkinson’s disease, said: “We looked at the properties of millions of antibodies and compared them with human proteins found inside the cell.
“From this we figured out that antibodies usually 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 are super stable.”
The researchers say the findings could help scientists unlock new uses for the millions of antibodies that have already been developed over decades of biomedical research.
The study shows these antibodies can now potentially be repurposed both as powerful research tools and as the basis for future treatments targeting disease-causing proteins.
Dr Wright, who directed the research, believes the work could have a significant impact on tackling serious diseases that affect tens of millions of people worldwide.
“We’ve made intracellular antibodies that stick to proteins that cause neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and motor neurone disease,” said Dr Wright.
“These diseases can lead to cognitive impairment, forgetfulness, loss of muscle control and death. They affect over one million people in the UK alone, so they are a big public health concern.
“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 medicine discovery process.”
The work was praised by the MND Association.
Chief Scientist at the charity, Dr Brian Dickie, said: “Dr Wright and his colleagues have made a significant advance in overcoming one of the key challenges that has impeded the development of antibodies as treatments for neurodegenerative diseases, such as MND.
“Their research findings provide optimism that a combination of this novel ‘intrabody’ science with emerging gene therapy techniques may lead to new therapeutic strategies that can hit specific molecular targets within neurones.”
END
Using artificial intelligence, an international team of scientists has created tiny antibody fragments that can be made directly inside human cells, where they bind to proteins linked to disease.
Normally, antibodies can only function outside cells.
But these redesigned fragments, known as intrabodies, are engineered to survive inside cells and target the proteins that drive neurodegenerative conditions.
The MND Association-funded research, led by Dr Caitlin O’Shea and Dr Gareth Wright from the School of Life Sciences, found that electrical charge plays a crucial role in whether these antibody fragments remain stable and usable inside cells.
By combining that knowledge with AI-based protein redesign, the researchers were able to convert 672 different antibodies into intrabodies that target key disease-related proteins.
The work could help researchers develop new tools and therapies that act directly inside living cells, where many neurodegenerative diseases begin.
These redesigned molecules will be made freely available to other scientists now the research has been published in Nature Communications.
Lead author Dr O’Shea, who specialises in MND and Parkinson’s disease, said: “We looked at the properties of millions of antibodies and compared them with human proteins found inside the cell.
“From this we figured out that antibodies usually 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 are super stable.”
The researchers say the findings could help scientists unlock new uses for the millions of antibodies that have already been developed over decades of biomedical research.
The study shows these antibodies can now potentially be repurposed both as powerful research tools and as the basis for future treatments targeting disease-causing proteins.
Dr Wright, who directed the research, believes the work could have a significant impact on tackling serious diseases that affect tens of millions of people worldwide.
“We’ve made intracellular antibodies that stick to proteins that cause neurodegenerative diseases such as Alzheimer’s, Parkinson’s, Huntington’s and motor neurone disease,” said Dr Wright.
“These diseases can lead to cognitive impairment, forgetfulness, loss of muscle control and death. They affect over one million people in the UK alone, so they are a big public health concern.
“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 medicine discovery process.”
The work was praised by the MND Association.
Chief Scientist at the charity, Dr Brian Dickie, said: “Dr Wright and his colleagues have made a significant advance in overcoming one of the key challenges that has impeded the development of antibodies as treatments for neurodegenerative diseases, such as MND.
“Their research findings provide optimism that a combination of this novel ‘intrabody’ science with emerging gene therapy techniques may lead to new therapeutic strategies that can hit specific molecular targets within neurones.”
END
Attachments
