Fla. — Researchers on Mayo Clinic’s Florida campus have
identified key differences between patients with sporadic
amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease)
and those with the most common genetic form of ALS, a mutation
in the C9orf72 gene.
findings, recently reported online in Nature Neuroscience,
demonstrate that ALS patients show abnormalities in levels and
processing of ribonucleic acids (RNA), biological molecules
that determine what gene information is used to guide protein
than 30,000 Americans live with ALS, a condition that destroys
motor neuron cells that control essential muscle activity,
such as speaking, walking, breathing and swallowing. While
increasing efforts are geared toward therapeutic development,
an effective drug for ALS has yet to be identified, in large
part because of our incomplete understanding of the disease.
results using advanced, modern laboratory techniques called
next-generation sequencing, allowed us to acquire a library of
new knowledge about patients with ALS," says the study’s
senior author, Leonard Petrucelli, chair of the Department of
Neuroscience at Mayo Clinic’s Florida campus.
Petrucelli and Hu Li, assistant professor of pharmacology at
Mayo Clinic’s campus in Rochester, Minn., led a team of
investigators who carefully analyzed the RNA from human brain
tissues. They found that ALS brains had numerous RNA defects,
compared to non-diseased brains. They also predicted molecular
events that may be altered due to the changes found in RNAs
involved in pathways regulating those events and that may
contribute to ALS.
the researchers observed some commonalities, they also found
many distinctions between the RNAs that were altered in
sporadic versus C9orf72 mutation-associated cases. This
suggests there may be different factors contributing to ALS in
patients. The success of future therapies may need specific
tailoring to the specific root cause of a patient’s motor
neuron disease. Furthermore, the large volume of data obtained
from their study, which was deposited into a public genomics
data repository, provides a wealth of information available to
other researchers to accelerate ALS research.
the success of their study was procuring samples from
individuals who generously donated their tissues for research
purposes to the Mayo Clinic after their passing.
year, the ALS Ice Bucket Challenge raised a remarkable amount
of money to support ALS patients and research," Dr.
Petrucelli says. "Without the extreme generosity of both
monetary donors and patient tissue donors we could not make
these strides in understanding this devastating disease."
Petrucelli laboratory is conducting follow-up studies based on
the data from this study to determine which alterations are
important in ALS pathogenesis. The researchers also will study
which alterations should be developed as diagnostic and
prognostic biomarkers or as therapeutic targets that may offer
hope to patients with ALS.