Angelman syndrome is a genetic disorder that delays neurological development. It is commonly found in infants and is often mistaken as autism or cerebral palsy due to the intellectual and developmental delays that the disorder causes. Children with Angelman syndrome appear to be hyperactive and display uncoordinated movements, and also have evident speech impairment and frequent seizures throughout their lives.
The syndrome is caused by the loss of a functional copy of the gene UBE3A, found on chromosome 15.
|(Angelman Syndrome, 2011)|
The protein which UBE3A produces is vital for aiding brain neurons to pass electrical or chemical signals to other neurons. Normally a copy of UBE3A is inherited from each parent and both genes are activated in various parts of the body. In the brain, however, the gene acts as imprinted genes, where only one parents copy of the gene is activated while the other is dormant. In this case it is the maternal copy of the gene which is activated. In a child who is effected by Angelman syndrome, the protein that UBE3A produces is missing, resulting in the severe neurological problems which define the syndrome.
There are several genetic defects which may occur in the UBE3A gene which causes Angelman syndrome. The main cause is due to the deletion of a specific segment of chromosome 15, where the UBE3A gene is located. (Bernard, D. 2012) In most other cases the defect is caused by a faulty sequence of DNA in the UBE3A gene, which is commonly referred to as a mutation.
Current research being conducted on Angelman syndrome has one main aim, to restore gene activity and to activate the non-functional copy of the paternal UBE3A gene. (Saey, TH. 2012) The repression of the paternal UBE3A gene is caused by “antisense RNA” (Malpass, K. 2011), a ribonucleic acid which functions to suppress genes such as the allele of UBE3A. It does so by binding to the RNA of the gene, and therefore blocking the process of translation resulting in no protein production. (Antisense RNA, 2011)
Like humans, rodents do not have the active form of paternal UBE3A in their brain, therefore clinical trials were done on rodents to identify if a certain drug could activate this gene. Eventually it was discovered that the drug Irinotecan, a topoisomerase inhibitor (Saey, TH. 2012) could activate UBE3A genes in rodents that presented with Angelman syndrome. The drug normally inhibits DNA-unwinding and alters DNA so that it can no longer undergo replication, and is therefore used for treatment of cancer cells. In the clinical tests, however, it activated the UBE3A gene by reducing the amount of antisense RNA bound to the paternal copy of UBE3A. Not only could the anticancer drug activate the dormant UBE3A allele, but also the protein produced from the now functional UBE3A gene was both functional and equivalent to the average amount of protein produced in a control. (Malpass, K. 2011)
It is not yet sure whether or not the drugs can restore UBE3A production in human brain cells, or if there are long term side effects from using the cancer fighting drugs. The idea has to undergo many tests before it can be clinically tested on humans. But so far the results prove that some anticancer drugs such as Irinotecan can activate the dormant UBE3A gene in brain cells and although the research is very recent, the results do show hope for a cure of Angelman Syndrome.
Angelman Syndrome, 2011. Viewed 16 March 2012, <http://ghr.nlm.nih.gov/condition/angelman-syndrome>
Antisense RNA, 2011. Viewed 19 March 2012,
Bernard, D. 2012. Clinical Summary of Breakthrough in Angelman Syndrome Research, Viewed 18 March 2012, <http://www.angelmansyndrome.org/PDF_files/clinical%20summary%20breakthrough%20070212.pdf >
Malpass, K. 2011 ‘Neurodevelopmental disorders: Unsilencing dormant UBE3A – hope for Angelman Syndrome?’, Nature Reviews Neurology, vol. 62, no.8, viewed 14 March 2012, <http://news.unchealthcare.org/news/2011/december/unc-study-could-lead-to-a-treatment-for-angelman-syndrome>
Saey, TH. 2012 ‘Drugs Activate Dormant Gene’, Science News, vol.181, no.2, pp.8 <www.sciencenews.org/view/generic/id/337083/title/Drugs_activate_dormant_gene >