Scientists tackle Huntington's disease by targeting mutant gene

November 6, 2012, CORDIS
Scientists tackle Huntington's disease by targeting mutant gene
Credit: Shutterstock

Huntington's disease is an inherited, neurodegenerative disorder that usually appears in mid-adult life and leads to uncoordinated body movements and cognitive decline. The disease is due to multiple repetitions of a deoxyribonucleic acid (DNA) sequence (i.e. the nucleotides CAG) in the gene encoding the 'Huntingtin' protein. This sequence is present more than 35 times in patients suffering from this disease, while it is repeated 10 to 29 times in healthy patients. In a recent study, published in the journal PNAS, researchers in Spain succeeded in reducing the chromosomal expression of the mutant gene, which could potentially hinder disease development.

Researchers say adult humans specifically need the Huntingtin protein, which is located in different tissues of the body, to ensure the development and survival of neurons. The presence of a results in an abnormal form of the Huntingtin protein. When this happens, the body is affected by a number of symptoms, including involuntary movements, behavioural changes and dementia. Despite inroads made into this condition, no one has been able to find a cure for Huntington's disease. Patients are currently treated to ease their pain and discomfort, and most patients die around 15 years after their symptoms first appear.

Scientists know that one gene is responsible for Huntington's disease, which is not the case for other neurological disorders like Parkinson or Alzheimer. So they are hopeful that developing a therapy based on the inhibition of the mutant Huntingtin gene could lead to the development of a treatment for it. Current studies focus on the modification of proteins that are contained in all living beings, such as the proteins (ZFP) that have the ability to recognise and bind to specific . Briefly, this process results in a regulated gene function.

Researchers from the CRG took their work one step further by reducing the chromosomal expression of the mutant gene, potentially hindering the development of the disease.

'We designed specific ZFP that recognize and specifically bind to more than 35 repetitions of CAG triplet, preventing the expression of the gene containing these repeats and reducing the production of the mutant ,' said lead author Mireia Garriga-Canut, a researcher from the Gene Network Engineering group at the CRG. 'When applying this treatment to a transgenic mouse model carrying the human mutant , we observed a delayed onset of the symptoms.'

Carmen Agustín Pavón, one of the authors of the study, said, 'The next step is to optimise the design for an effective and durable treatment for patients. This would pave the way to find a therapy for Huntington's disease.'

Explore further: A step toward controlling Huntington's disease?

More information: Garriga-Canut, M., et al., 'Synthetic zinc finger repressors reduce mutant Huntingtin expression in the brain of R6/2 mice', PNAS, 2012. doi:10.1073/pnas.1206506109

Related Stories

A step toward controlling Huntington's disease?

June 23, 2011
Johns Hopkins researchers have identified a natural mechanism that might one day be used to block the expression of the mutated gene known to cause Huntington’s disease. Their experiments offer not an immediate cure, ...

Proposed drug may reverse Huntington's disease symptoms

June 20, 2012
With a single drug treatment, researchers at the Ludwig Institute for Cancer Research at the University of California, San Diego School of Medicine can silence the mutated gene responsible for Huntington's disease, slowing ...

New insight into the cellular defects in Huntington's disease

October 10, 2011
Huntington disease is a devastating neurogenerative disorder that causes a progressive loss of functional capacity and reduced life span. It is an inherited condition caused by a mutant HTT gene. Although this has been known ...

Recommended for you

Peers' genes may help friends stay in school, new study finds

January 18, 2018
While there's scientific evidence to suggest that your genes have something to do with how far you'll go in school, new research by a team from Stanford and elsewhere says the DNA of your classmates also plays a role.

A centuries-old math equation used to solve a modern-day genetics challenge

January 18, 2018
Researchers developed a new mathematical tool to validate and improve methods used by medical professionals to interpret results from clinical genetic tests. The work was published this month in Genetics in Medicine.

Can mice really mirror humans when it comes to cancer?

January 18, 2018
A new Michigan State University study is helping to answer a pressing question among scientists of just how close mice are to people when it comes to researching cancer.

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.