Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

A cross-departmental collaboration involving Associate Professor Esther Becker and Lauren Watson, a research scientist in the Becker group, has led to the publication of an important paper reporting dominant mutations that cause spinocerebellar ataxias. 

Spinocerebellar ataxias are a group of diseases that cause degeneration in the cerebellum, which is the part of the brain responsible for controlling movement. Whilst there many different types of this disorder, each with their own unique symptoms, generally the disorder is characterised by problems with movement that worsen over time. 

The paper, published in the American Journal of Human Genetics, describes a series of mutations in a human gene called GRM1, which produces a glutamate receptor known as mGlur1. mGlur1 is one of the most abundant of its group of receptors in the Central Nervous System and is particularly rich in the group of brain cells in the cerebellum known as Purkinje cells. Disease causing mutations in GRM1 are quite rare.; however, a single family with recessive mutations has been identified as causing cerebellar ataxia and intellectual disability.

This paper has now identified, for the first time, dominant mutations in GRM1 that cause distinct disease symptoms. Two of the mutations led to increased receptor activity and caused slowly progressive ataxia with disease onset between the ages of 20 and 50. These families did not carry any other known spinocerebellar ataxia-causing mutations. The team also identified another mutation occurring in a child, whose parents were unaffected, that led to the production of a shorter form of the protein. This caused intellectual disability and cerebellar ataxia without apparent shrinking of the cerebellum.

The finding of mutations that lead to increased receptor activity are particularly important because drugs are available that have the opposite effect, reducing activity. The researchers tested an approved mGluR1 drug Nitazoxanide against these mutant receptors in laboratory conditions.  Nitazoxanide was indeed shown to inhibit the mutant receptor in these experiments.  This offers the hope that drugs targeting mGlur1 may one day offer therapeutic opportunities in cerebellar ataxias.

To find out more about the work that goes on in the Becker Group, visit their webpage.  

Similar stories

Can humans hibernate?

Illuminating new TEDx Talk from Professor of Sleep Physiology Vladyslav Vyazovskiy

New insights into chemogenetic designer drugs to enhance our study of behaviour

A collaborative team of researchers in DPAG and Pharmacology led by Dr Lukas Krone have uncovered striking new data demonstrating that two widely used designer drugs used to turn populations of neurons on and off in the brain cause unexpected effects on sleep. These results demonstrate a critical need to improve chemogenetic approaches in behavioural studies.

Unlocking the Secrets of cAMP Signalling in the Heart: A Pathway to Targeted Therapeutics

A new Zaccolo group study has revealed key new insights into the role of cAMP signalling in both healthy and disease settings within the heart. They have identified new cAMP nanodomains in cardiac muscle cells that have far reaching implications for the treatment of heart disease.

Key exosome subtype in cancer progression identified

Collaborative work from DPAG and Oncology researchers has revealed a potential new pathway to block the production of a specific group of exosomes made in the cell’s recycling system that can promote the growth of cancerous tumours.

New blood test from DPAG cardiac researchers could save lives of heart attack victims

Researchers from the Herring group have developed a blood test that measures stress hormone levels after heart attacks. The test – costing just £10 – could ensure patients receive timely life-saving treatment.