A team of researchers from the US-based University of North Carolina has identified a potential treatment for a rare genetic disorder -- 'Angelman syndrome', a new study said on Monday.
Angelman syndrome is caused by mutations in the
maternally inherited UBE3A gene and is characterised by poor muscle control,
limited speech, epilepsy, and intellectual disabilities, explained researchers
in the study published in the journal Nature Communications.
Ben Philpot, PhD, the Kenan Distinguished
Professor at the UNC School of Medicine, and his lab have identified a small
molecule that could be safe, non-invasively delivered, and capable of 'turning
on' the dormant paternally-inherited UBE3A gene copy brain-wide, which would
lead to proper protein and cell function, amounting to a kind of gene therapy
for individuals with Angelman syndrome.
"This compound we identified has shown to
have excellent uptake in the developing brains of animal models," said
Philpot, who is a leading expert on Angelman syndrome.
As per researchers, UBE3A helps regulate the
levels of important proteins; missing a working copy leads to severe
disruptions in brain development.
The researchers screened over 2,800 small
molecules to determine if one could potently turn on paternal UBE3A in mouse
models with Angelman syndrome.
They found that a compound -- (S)-PHA533533,
which was previously developed as an anti-tumour agent, caused neurons to
express a fluorescent glow that rivalled that induced by topotecan, meaning
that its effect was potent enough to successfully turn on paternal UBE3A.
Researchers were able to confirm the same
results using induced pluripotent stem cells derived from humans with Angelman
syndrome, indicating that this compound has clinical potential, the study
mentioned.
In addition, they observed that (S)-PHA533533
has excellent bioavailability in the developing brain, meaning it travels to
its target with ease and sticks around.
"We were able to show that (S)-PHA533533 had better uptake and that the same small molecule could be translated in human-derived neural cells, which is a huge finding," said Hanna Vihma, PhD, and first author of the study.
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