Scientists tackle Huntington's disease by targeting mutant gene

November 6, 2012 in Genetics

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.'

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

Journal reference: Proceedings of the National Academy of Sciences search and more info website

Provided by CORDIS search and more info website

5 /5 (1 vote)  

Rank 5 /5 (1 vote)
Relevant PhysicsForums posts

More news stories

Researchers identify first drug targets in childhood genetic tumor disorder

Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...

Genetics created May 24, 2013 | popularity 3 / 5 (2) | comments 0 | with audio podcast

Patenting the human genome

Can human genes be patented? That was the question posed by Alan J. Snyder, vice president and associate provost for research and graduate studies at Lehigh, and Lee Kaplan, scientific director of cellular and molecular genetics ...

Genetics created May 24, 2013 | popularity 4 / 5 (1) | comments 0

Researchers complete largest genetic sequencing study of human disease

Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.

Genetics created May 22, 2013 | popularity 4.5 / 5 (4) | comments 0 | with audio podcast

Researchers develop model for better testing, targeting of malignant peripheral nerve sheath tumors

University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...

Genetics created May 20, 2013 | popularity 5 / 5 (1) | comments 0 | with audio podcast

Researchers identify new circadian clock component

Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.

Genetics created May 16, 2013 | popularity 3 / 5 (1) | comments 1 | with audio podcast


First drug to improve heart failure mortality in over a decade

Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...

Seniors more likely to crash when driving with pet, study finds

(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...

Heart failure accelerates male 'menopause'

Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...

Death highest in heart failure patients admitted in January, on Friday, and overnight

Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...

Feds fight morning-after pill age ruling in NY

(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...

New immune system discovered

(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.