Ataxia, a neurodegenerative disorder has no known cure. It
often occurs when parts of the nervous system that control movement are
damaged. People with ataxia experience a failure of muscle control in
their arms and legs, resulting in a lack of balance and coordination or a
disturbance of gait, suggested the National Institute of Neurological Disorders and Stroke.
According to a recent study published in JAMA Neurology
Northwestern Medicine scientists have examined more than a century of
data of the genetic makeup of ataxias to
better understand the different forms of this devastating disease and
how it affects patients. This research has the potential for scientists
to have a better understanding on how to diagnose and treat the disease.
‘Being able to better understand the genetic diversity of ataxia allows us to gain insight on a system level into genes and cellular pathways that result in neurodegeneration.’
"More than 150,000 Americans
suffer from hereditary or sporadic ataxia in the United States and
being able to better understand the genetic diversity allows us to gain
insight on a system level into genes and cellular pathways that result
in neurodegeneration," said Puneet Opal, neurologist at Northwestern Memorial Hospital.
better diagnose and treat patients with ataxia, co-authors Opal and
former Northwestern Medicine researcher and current University of
California San Francisco School of Medicine adjunct professor Alessandro
Didonna reviewed the genetic makeup of ataxias syndrome and the
use of genetic sequencing and computer driven bioinformatics over the
last 150 years.
With the major advances in gene sequencing, a
clearer understanding of ataxias through The Human Genome Project, the
first successful undertaking to precisely sequence the human genetic
code by solving the three billion "letters" in human DNA, and next
generation sequencing (NGS), first commercially available sequencing
technology that helps to identify genes with underlying genetic
syndromes, helps provided additional insight on ataxia.
Genome Project was launched in 1998 to be able to read nature's
complete genetic blueprint for building a human being. The ability to
catalog the first full human DNA sequence inspired another approach for
genome analysis called NGS which became available to researchers in
2007. This technology allowed scientists to make large scale whole
genome sequencing through a computerized system that is faster, more
in-depth and cost-effective.
The co-authors also discovered that
cellular pathways and protein networks in ataxias exist in the genes.
This discovery helped to better understand how aging plays a role in the
risk for neurogenerative diseases like ataxia. In addition, scientists
compared ataxia with other diseases and found a link with Alzheimer,
Parkinson, and Huntington disease. Scientists now know that ataxias can
be inherited by all modes of Mendelian inheritance with mutations in
more than 70 genes responsible for autosomal recessive ataxias,
approximately 40 autosomal dominant ataxias, six X-linked genes, and three
mitochondrial - all of which are subtypes of hereditary ataxias.
number is likely to increase," said Opal. "However, we are quickly
closing the gap in understanding the cause of neurodegeneration.
Moreover, we know that genetically different ataxia syndromes converge
to cellular pathways that we hope will help generate rationale drugs
that can attack these pathways and eventually provide personalized
medicine for patients diagnosed with this disease."
As part of the
ongoing efforts, the co-authors of the study will be examining the
complexities of the genetic mutation in ataxias syndrome hoping to
discover more types of ataxias that are still uncharacterized.