This article is more than 5 years old. Information may no longer be current.
Topotecan may be therapeutic for Angelman, Prader-Willi syndrome
Click Here to Manage Email Alerts
Recent data suggest that a chemotherapy agent used to treat metastatic cancers may also be therapeutic for Angelman or Prader-Willi syndrome, according to researchers.
“What determines whether you have Prader-Willi syndrome or Angelman syndrome is whether the maternal or paternal gene is missing,” Janine M. LaSalle, PhD, of the Medical Microbiology and Immunology, Genome Center, MIND Institute at the University of California, Davis, said in a press release. “These are the classic, textbook epigenetic disorders involving parental imprinting. It’s not just about the chromosomes, but it’s where — or who — they come from. In our study, we show that R-loops forming on the active paternal chromosome within the Prader-Willi region regulate imprinting of the Angelman gene, Ube3a, on the maternal chromosome.”
LaSalle and colleagues wrote that topotecan stabilized the arrangement of R-loops, or RNA:DNA hybrids, at G-skewed repeat elements within the paternal gene Snord116. This increases the loosening of chromatin and suppression of Ube3a-ATS expression, they added.
Furthermore, neural precursor cells from paternal Snord116 deletion mice demonstrated an increase in Ube3a-ATS levels in different neurons, and led to the reduction of topotecan’s effects compared with wild-type neurons, researchers wrote.
“Now we have a molecular mechanism for a proposed drug for a disease, so we can understand how it works and begin to tweak it to develop therapies,” researcher Weston T. Powell, PhD, also of the Medical Microbiology and Immunology, Genome Center, MIND Institute at the University of California, Davis, said in a press release.
Disclosure: The researchers did not specify relevant financial disclosures.
Collapse
Click Here to Manage Email Alerts