information on the molecular mechanisms that cause Huntington's disease has been published by a group of scientists from the Center
for Genomic Regulation (CRG) led by EulÓlia MartÝ, in cooperation with
researchers from the University of Barcelona (UB) and August Pi i Sunyer
Biomedical Research Institute (IDIBAPS).
Huntington's disease is a neurodegenerative disease that is presently
incurable. Scientists around the world are researching its causes and
molecular processes in the attempt to find a treatment.
‘Blocking the activity of messenger RNA (the "conveyor"), would be enough to revert the alterations associated with Huntington's disease.’
The results of the study
are published in the November issue of the Journal of Clinical Investigation
. EulÓlia MartÝ is the lead author, while Laura RuÚ and Mˇnica Ba˝ez are its first authors.
Huntington's disease is caused by the excessive repetition of a
nucleotide triplet (CAG) in the Huntingtin gene. The number of CAG
repetitions varies from person to person. Healthy individuals can have
up to 36 repetitions. Nevertheless, as of 36 repetitions, Huntington's
disease develops. The direct consequence of this excess of repetitions
is the synthesis of a mutated protein-different from what would be
obtained without the additional CAG repetitions-which has been
considered the main cause of the disease for the past 20 years.
"What we have observed in our study is that the mutated fragment
acting as a conveyor-the so-called messenger RNA-is key in the
pathogenesis," says Dr. EulÓlia MartÝ, lead author of the research
project, together with Xavier Estivill, and acting group leader of the
Genes and Disease laboratory at the Center for Genomic Regulation.
research on this disease being done by most groups around the world
seeking new therapeutic strategies focuses on trying to prevent
expression of the mutated protein. Our work suggests that blocking the
activity of messenger RNA (the "conveyor"), would be enough to revert
the alterations associated with Huntington's disease. We hope this will
contribute to improving the strategies in place to find a cure," states
Going deeper in molecular mechanisms enables progress to future applications
This work underscores the importance of rethinking the mechanisms
behind illnesses in order to find new treatments. The work of scientists
at the CRG has helped explore the molecular mechanisms that cause the
disease. Now, their results will contribute to better delimit research
efforts towards a cure.
As opposed to most other research groups, EulÓlia MartÝ's team has
sought to identify whether the problem resided in the messenger RNA -
which would be the copy responsible for manufacturing the protein - or
in the resulting protein. Prior work indicated that mRNA produced, in
addition to defective protein, other damages.
This previous work was the
starting point for MartÝ and her fellow researchers, who have finally
demonstrated that mRNA has a key role in the pathogenesis of
Huntington's chorea. "The research we have just published points to
RNA's clear role in Huntington's disease. This information is very
important in translational research to take on new treatments," says the
More in-depth studies on these mechanisms are yet to be done. For
example, research must explore whether it will be possible to revert the
effects of Huntington's disease in patients, just as researchers have
demonstrated in mouse models. It also remains to be seen whether the
proposal of the CRG researchers can be used in a preventive way, as the
disease does not generally appear until after 40 years of age (in
humans). Despite the remaining gaps, the published work makes for a key
step in knowledge of the mechanisms of this neurodegenerative disease
that, as of today, remains incurable.