Experimental Therapy For Rare, Incurable Disease Prader-Willi Syndrome Looks Promising, Says Study
Activating a set of silenced genes with the help of drugs helped in improving growth and survival of mice model with Prader-Willi Syndrome, reports a recent study.
Prader-Willi Syndrome In Children
PWS is a genetic disorder that causes incurable obesity in children. It is estimated that one in 15,000 to 25,000 children born alive in the country is affected by the life-threating obesity syndrome. Both male and female children are equally prone to PWS. Children affected by the syndrome have difficulty in eating and experience debilitating behavioral, psychiatric, physical and intellectual symptoms.
Generally, genetic information from parents is passed to children through a pair of chromosome – one each from the couple. Children with PWS exhibit defect in a region of the chromosome obtained from the male parent.
Genetics Behind Prader-Willi Syndrome
Genetic alterations in the segment called Prader-Willi critical (PWC) region in chromosome 15 result in PWS. Normally, genes present in the PWC region of the maternal chromosome are not expressed in any individual. They are silenced or inactive in nature. However, similar genes in the paternal chromosome are active in healthy people unlike individuals with PWS.
Due to genetic changes in the paternal PWC region, people with PWS carry inactive genes and in some cases the genes would be missing altogether. Infants with the syndrome don't grow as healthy as other children and also experience difficulty in eating and other metabolic functions. In contrast, the children experience compulsive eating disorder as they grow.
Drugs UNC0642 And UNC0638 For Prader-Willi Syndrome Treatment
In the study supported by the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development, the researchers used two drugs – UNC0642 and UNC0638 – to activate the silenced PWS genes in the maternal chromosome in the cells obtained from an affected person.
The research team focused on the UNC0642 drug since it displayed better pharmacological results in the mice model with PWS. Similar to infants with PWS, the PWS mice show poor growth and don't survive beyond a stage.
When the drug was tested in the PWS mice model, the mice were observed to have gained weight and displayed better growth than the untreated PWS mice. And about 15 percent of the mice survived into adulthood without serious side effects.
The drugs developed by the researchers work by blocking the functions of G9a protein, which along with other proteins, keeps the maternal genetic material intact in the chromosome.
"Overall, the study shows that this type of therapy may be beneficial for treating PWS, but researchers will need to evaluate the drugs' effects on other disease symptoms, such as compulsive overeating and obesity," the ressearchers reported in a press release.
The study is published in the journal Nature Medicine.