This is a rare genetic
disorder that is characterized by poor muscle tone, low level of sex
hormone and extreme hunger. The feeling of fullness of satiety response is poor
in people with this disorder resulting in overeating and obesity.
‘First ever treatment for Prader Willi syndrome offers hope to the many affected by the condition. A drug like molecule that inhibits G9a, an enzyme that is important for gene regulation has been found.’
classic symptoms of this disorder include:
- Floppiness and an
inability to suck in newborns
- Poor motor skills
- Weight gain
- Mild learning
There is no known cure for this condition
and obesity is controlled using exercises and diet. People with this condition
need to be monitored for the rest of their lives and need special support.
Potential Treatment in
majority of the cases of Prader-Willi
syndrome, the individual gets a copy from the mother that is silent
while the gene copy in chromosome 15 is missing from the father. Under normal
circumstances, the gene in the father's copy of the chromosome would carry out
the necessary function, however, since this gene is missing, the researchers
from Duke University tried to activate the silent gene from the mother to carry
out the functions.
Bryan Roth from The University of North Carolina and colleagues screened more
than 9,000 compounds which could activate the silent gene. Fluorescent markers
were used to identify whether any of the compounds triggered the cells to glow,
indicating that the compound successfully activated the silent gene.
A class of molecules called the G9a inhibitors
was successful in both mouse models as well as in the human cells from patients
with the disorder. The enzyme G9a is important in gene regulation
that were treated with the G9a inhibitors during the stage of infancy showed
normal development and lived longer. Dr. Yong-hui Jiang, who is an associate
professor in Duke's departments of Pediatrics and Neurobiology said "Our
findings suggest that G9a inhibitors may play a role in regulating the
silencing of parental chromosomes on certain genes that require an imprinting
process for normal function. This could provide a new insight for the molecular
mechanism of genomic imprinting."
a study published by Ana Fiszbein et al in the journal Cell Reports
, it was found that alternate splicing of G9a lead to
neuronal differentiation. G9a is an important enzyme that is required for
neuron differentiation. This important enzyme has been implicated in the growth
and differentiation of a variety of cells and tissues, including thenocytes and
skeletal muscles. In the nervous system it has been found that G9a controls
cognition as well as controlling adaptive responses by repressing non neuronal
the study by Chen WL and colleagues titled "G9a- An antineoplastic target"
published in the Journal Current Cancer
, the mounting evidence of G9a catalyzing histone and
non-histone proteins are detailed. Another study by Fransesco Casciello titled
"Functional Role of G9a Histone Methyltransferase in Cancer" published in the
Journal Frontiers in Immunology
focusses on the gene regulation of G9a and its role in cancer progression and
differentiation. G9a inhibition is found to inhibit cell proliferation in many
cell lines and its presence is found to increase growth and proliferation of
The study on Prader Willi syndrome is one of the
first few studies that focus on the treatment for this rare genetic disorder.
If the animal studies can be replicated in human studies, then the compound
used to inhibit G9a could be an effective means of treatment for Prader Willi,
the very first treatment for this condition.
from Prader Willi syndrome, the G9a inhibitor identified in the current study
can be used for other similar
genetic disorders. The
incidence of Prader Willi syndrome is only 1 in 15,000 but it can result in shorter life span and greater dependency on caregivers for
The identification of the drug like compound that inhibits G9a
enzyme could help treat the condition and lead to a longer lifespan with a
better quality of life.
- Functional Role of G9a Histone Methyltransferase in Cancer -
- Prader-Willi Syndrome -
- Yuna Kim, Hyeong-Min Lee, Yan Xiong, Noah Sciaky, Samuel W Hulbert, Xinyu Cao, Jeffrey I Everitt, Jian Jin, Bryan L Roth, Yong-hui Jiang. Targeting the histone methyltransferase G9a activates imprinted genes and improves survival of a mouse model of Prader-Willi syndrome. Nature Medicine, 2016; DOI: 10.1038/nm.4257