The molecular basis of Huntington's disease | The Royal Society
Join us for the Royal Society Ferrier Prize Lecture delivered by Professor Gillian Bates FRS.
Professor Gillian Bates FRS is awarded the Ferrier Medal 2025 for her work in understanding the molecular basis of Huntington’s disease and consistently producing highly impactful findings which have moulded the course of this field.
This talk covers how in 1993, the mutation that causes Huntington’s disease, a devastating neurodegenerative disorder, was found to be an extra-long CAG repeat in exon 1 of the huntingtin gene (HTT) that encodes a polyglutamine tract in the HTT protein. Over the last 30 years, the Bates lab has been unravelling the first molecular steps by which the mutation causes neuronal dysfunction and neurodegeneration. The mutant CAG repeat is unstable, expanding in specific neuronal cells with age, and the rate of this somatic expansion is known to drive the age of disease onset and rate of disease progression. The Bates lab have found that the mutant HTT pre-mRNA is alternatively processed to generate the small HTT1a transcript, the longer the CAG repeat, the more HTT1a is produced. This encodes the aggregation prone HTT1a protein, that they have shown to be highly pathogenic, representing the second step in the pathogenic cascade. Their recent preclinical studies demonstrate that lowering the HTT1a transcript is much more effective than lowering full-length HTT and may explain the failure of a large huntingtin-lowering clinical trial. Their data indicates that huntingtin-lowering strategies should be designed to target the HTT1a transcript.
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Professor Gillian Bates FRS is awarded the Ferrier Medal 2025 for her work in understanding the molecular basis of Huntington’s disease and consistently producing highly impactful findings which have moulded the course of this field.
This talk covers how in 1993, the mutation that causes Huntington’s disease, a devastating neurodegenerative disorder, was found to be an extra-long CAG repeat in exon 1 of the huntingtin gene (HTT) that encodes a polyglutamine tract in the HTT protein. Over the last 30 years, the Bates lab has been unravelling the first molecular steps by which the mutation causes neuronal dysfunction and neurodegeneration. The mutant CAG repeat is unstable, expanding in specific neuronal cells with age, and the rate of this somatic expansion is known to drive the age of disease onset and rate of disease progression. The Bates lab have found that the mutant HTT pre-mRNA is alternatively processed to generate the small HTT1a transcript, the longer the CAG repeat, the more HTT1a is produced. This encodes the aggregation prone HTT1a protein, that they have shown to be highly pathogenic, representing the second step in the pathogenic cascade. Their recent preclinical studies demonstrate that lowering the HTT1a transcript is much more effective than lowering full-length HTT and may explain the failure of a large huntingtin-lowering clinical trial. Their data indicates that huntingtin-lowering strategies should be designed to target the HTT1a transcript.
The Royal Society is a Fellowship of many of the world's most eminent scientists and is the oldest scientific academy in continuous existence.
▶https://royalsociety.org/
?Subscribe to our channel for exciting science videos and live events, many hosted by Brian Cox, our Professor for Public Engagement: https://bit.ly/3fQIFXB
We’re also on Twitter ▶ https://twitter.com/royalsociety
Facebook ▶ https://www.facebook.com/theroyalsociety/
Instagram ▶ https://www.instagram.com/theroyalsociety/
And LinkedIn ▶ https://www.linkedin.com/company/the-royal-society
The Royal Society
The Royal Society is a Fellowship of the world's most eminent scientists and is the oldest scientific academy in continuous existence.
We aim to recognise, promote, and support excellence in science and to encourage the development and use of science ...