Cachexia, a syndrome characterized by rapid weight loss and muscle deterioration, is a major cause of death among patients suffering from diseases like cancer, AIDS and chronic infection. Now, a newly published study by McGill University researchers shows that a low dose of Pateamine A is effective at preventing cancer-induced muscle wasting, which may lead to cachexia-fighting drugs.
Researchers from McGill block onset of cachexia in animal
models
Cachexia, a syndrome characterized by rapid weight loss and
muscle deterioration, is a major cause of death among patients
suffering from diseases like cancer, AIDS and chronic infection. In
fact, 30 per cent of cancer-related deaths are the result of
cachexia-induced muscle loss rather than the primary malignancy.
And while scientists are making strides in gaining a better
understanding of this deadly condition, no effective anti-cachectic
therapies exist to date. However, a newly published study by McGill
University researchers shows that a low dose of Pateamine A (PatA)
is effective at preventing cancer-induced muscle wasting – findings
that could someday point to the development of cachexia-fighting
drugs.
“To this day, when patients are diagnosed with cachexia, they’re
sent to palliative care. Their illness is no longer treatable. They
start losing muscle, including that which is in the lungs and they
eventually die by asphyxia,” explained Dr. Imed Gallouzi, the
paper’s senior author and Associate Professor in McGill’s Dept. of
Biochemistry and researcher at the Goodman Cancer Research Centre.
“It’s not that there are ineffective drugs out there, it’s that
there are no approved drugs to treat this condition right now.”
Recently, compounds like PatA, a natural derivative of marine
sponge known to interfere with protein production inside the cell
and Episilvestrol (Epi), a plant compound, have been found to block
tumor growth. Since tumors and inflammation are conditions that
lead to muscle wasting, Gallouzi and his team tested the effect of
different doses of PatA and Epi as potential anti-cachetic
agents.
“We observed that a low dose of PatA blocks the onset of muscle
wasting in two animal models by blocking the expression of factors
that promote cachexia,” said Gallouzi. “PatA was originally
identified as an inhibitor of the early steps that lead to protein
synthesis inside the cell. As such, however, PatA can be toxic.
Surprisingly, when we used this compound at a lower dose, we
observed that it prevents cachexia-induced muscle loss, by
specifically interfering with the expression of promoters of muscle
loss. Now we need to confirm that PatA, and its family of
compounds, is effective in blocking muscle wasting in other animal
models.”
The findings were published this week in the journal Nature
Communications. Co-lead authors are Sergio Di Marco and Anne
Cammas, both from McGill’s Dept. of Biochemistry and the Goodman
Cancer Research Centre (GCRC). Xian Jin Lian, Erzsebet Nagy Kovacs,
Jennifer F. Ma, Derek T. Hall (all from McGill Dept. of
Biochemistry/GCRC); Rachid Mazroui (Dept. of Molecular Biology,
Medical Biochemistry and Pathology, Centre de Recherche Hôpital
Saint-François d’Assise, Le CHUQ); John Richardson (McGill Dept. of
Neurology and Neurosurgery) and Jerry Pelletier (McGill Dept. of
Biochemistry/GCRC) also contributed to the work.