The paternally inherited copy of Ube3a is intact but silenced in neurons (grey neuron, green chromosomal region). Researchers are examining ways to activate the gene to ameliorate Angelman's syndrome.

A potential therapy for Angelman syndrome, a baffling genetic disease that impairs intellectual development, has been proposed by scientists including researchers at Isis Pharmaceuticals.

The treatment, tested in mice, activates a gene that restores some of the neurological activity reduced in Angelman syndrome, which affects an estimated 1 in 12,000 to 1 in 20,000 people.

A paper describing the research was published Dec. 1 in the journal Nature. The first authors are Linyan Meng of Baylor College of Medicine and Amanda J. Ward of Isis. Senior authors are Arthur L. Beaudet of Baylor and Frank Rigo of Isis. Seung Chun and C. Frank Bennett of Isis also authored the paper.

The therapy consisted of an antisense compound delivered to a mouse model of Angelman syndrome. Treated mice experienced less cognitive impairment than control mice, the study reported. Moreover, the scientists say they have developed a "clinically feasible" approach that may benefit people with the disorder.

Carlsbad-based Isis specializes in antisense drugs and is testing them in a wide range of diseases, including neurological ailments. The biotech company recently started a second Phase 3 trial of its drug for spinal muscular atrophy, a serious and sometimes fatal genetic disease that causes spinal motor neurons to die, reducing the ability to move.

A family describes life with a young boy who has Angelman syndrome.

Angelman children are characteristically happy, prone to frequent smiling and laughter. But they exhibit profound disabilities. They have reduced cognitive skills, either speak very little or not at all; have movement problems, may not be able to walk, sleep little, and often have seizures. The movement and mood features originally caused Angelman syndrome to be dubbed "happy puppet syndrome," a term that fell out of favor because of its disparaging overtones. Although they won't grow up to live independently, the children function at various levels.

The genetic cause of Angelman syndrome is loss of function in the maternally inherited copy of gene called UBE3A that's involved in neurological development. The paternal copy of the gene is silenced in neurons, due to imprinting, so if the mother's copy is missing the gene will not function at all in those neurons.

Loss of the maternal UBE3A gene's function can happen in several ways. The most common is deletion of a piece of chromosome 15 containing the gene. Other causes are mutation of the gene or a stretch of DNA called the imprinting center; or the child inherits two paternal copies of the gene and no maternal copy. Loss of the paternal UBE3A gene causes another neurological disorder, Prader-Willi syndrome.

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New Angelman syndrome therapy proposed

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