About Careers MedBlog Contact us

Take Away the 'Mute' from Silenced Gene to overcome Angelman Syndrome

by Himabindu Venkatakrishnan on December 2, 2014 at 8:55 PM
Font : A-A+

 Take Away the 'Mute' from Silenced Gene to overcome Angelman Syndrome

Inherited genes contain two working copies, one from the mother and one from the father. But sometimes, a gene is imprinted, meaning that one copy becomes silent. This is called genomic imprinting. If the active copy is mutated, then disease results, even though the silenced gene copy may be normal.

Angelman syndrome, which causes learning difficulties, speech problems, seizures, jerky movements and an unusually happy disposition, results when a gene inherited from the mother in a particular area of chromosome 15 is mutated and the other copy of the gene, inherited from the father, is silenced. In a report that appears online in the journal Nature Dr. Arthur Beaudet, professor of molecular and human genetics at Baylor College of Medicine and a clinical geneticist at Texas Children's Hospital, and colleagues answer the question: "Can we turn on the activity of the paternal gene?"


Angelman syndrome occurs when an infant inherits a mutated copy of the imprinted gene UBE3A from his or her mother. He or she also has a paternal copy of the gene, but it is silenced by a long ribbon of RNA called the UBE3A anti-sense transcript. (Antisense, in this case, is complementary to the ribbon of RNA, which means it binds to it and silences any activity.)

In an earlier experiment, Dr. Ben Philpott of the University of North Carolina showed that a type of drug called a topoisomerase could activate the father's copy of the gene, but the drug itself was toxic and it did not limit activation to the Angelman gene but affected all long genes.

One of Beaudet's graduate students - Linyan Meng - was writing her dissertation on Angelman syndrome and was wrestling with this problem when a member of her dissertation committee, Dr. Thomas Cooper, professor of pathology & immunology at Baylor, said he was working with a Carlsbad, Calif.-based company called Isis Pharmaceuticals that had anti-sense oligonucleotides that could turn off the antisense transcript that silenced the paternal copy of the gene. She bred a mouse in which the antisense transcript was "knocked down" and the paternal copy of the gene turned on.

"If you blocked the antisense, you could turn on the paternal copy," said Beaudet, also the Henry and Emma Meyer Chair in Molecular Genetics at Baylor. The treatment worked both in cells in the laboratory and in the live animals. The effect of the injection of the antisense oligonucleotides lasted about 16 weeks.

"It was clear from the molecular data that we were turning on the paternal copy of the gene," said Beaudet. "It is not clear how much we are able to reverse the behavioral abnormalities. "Studies in mice showed that the treatment appeared to reduce the cognitive deficits associated with Angelman syndrome. Yet more testing needs to be done.

"For the first time, we developed a sequence-specific and clinically feasible method to activate expression of the paternal Ube3a allele," said the authors in the report.

In the future, Beaudet said, researchers hope to see what happens if the gene is able to make even more protein. He anticipates that if the laboratory and animal studies continue to be positive, a study in children with the problem could be possible in the next two to three years. Perhaps, he said, the technique could be modified to work in other diseases that result from mutations in imprinted genes.

Source: Eurekalert


Recommended Reading

Latest Research News

What Are the Effects of T Cells on Blood Pressure and Inflammation?
A new study explored the link between T immune cells in ill patients and mortality risk.
How Does a New Procedure Help Patients Avoid Leg Amputation?
Limb savage procedure benefits patients with severe vascular disease who are at risk for amputation of their limbs.
Omega-3 Can Save Alzheimer's Patients from Vision Loss
Does omega-3 help Alzheimer's patients? A new form of omega-3 helped restore specific markers of eye health in mice bred with aspects of early-onset Alzheimer's disease.
Why Is Asthma Linked to Increased Risk of Osteoarthritis?
Drugs used to inhibit the physiological responses for allergic reactions lessen osteoarthritis risk, revealed research.
 Experiments on Child Brain Tumour and Muscle Ageing Heading to Space
The International Space Station will be used to carry out experiments seeking to improve understanding of incurable child brain tumors and the muscle aging process.
View All
This site uses cookies to deliver our services.By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use  Ok, Got it. Close

Take Away the 'Mute' from Silenced Gene to overcome Angelman Syndrome Personalised Printable Document (PDF)

Please complete this form and we'll send you a personalised information that is requested

You may use this for your own reference or forward it to your friends.

Please use the information prudently. If you are not a medical doctor please remember to consult your healthcare provider as this information is not a substitute for professional advice.

Name *

Email Address *

Country *

Areas of Interests