Jeffrey S. Buguliskis Ph.D. Technical Editor Genetic Engineering & Biotechnology News

Technology Advances and Increased Funding and Awareness Are Leading To New Revelations in the Neuroscience Field

Contained within the convoluted mass that resides in our skulls is not only the entirety of autonomic muscular signals that control our life-sustaining functions, but arguably more important, at least from an existential point of view, the chemo-electrical constituents that define every individual’s personality. Most often this is why the effects from neurologic disorders like Alzheimer’s disease and amyotrophic lateral sclerosis go far beyond the debilitating neurodegenerative symptoms and often dehumanize patients through the systematic eradication of their personality.

In relation to all other organ systems, our understanding of the brain and associated neuronal pathways is in its infancy. However, advances in technology, genetic analysis methods, and surges in funding and awareness have begun to create a critical mass of information that may well engender an array of revelations within the neuroscience field.

For instance, a recent project has begun to generate a comprehensive map of the neural connections within the brain by harnessing the power and speed of next-generation sequencing (NGS) technology. This task, dubbed the human connectome project, intends to not only create a brain wiring diagram, but also hopes to unlock some of the basic molecular mechanisms that underlie human cognition. Moreover, a rudimentary understanding of how neuronal cells interact is critical to comprehend what problems may arise within the brain and how we can develop better ways to screen for them.

“The next wave of new testing methodologies will provide even greater levels of resolution for less money,” explained Michael Friez, Ph.D., director of diagnostic laboratories at the Greenwood Genetic Center. “The greatest advances to be had will come in terms of new solutions to organizing, comprehending, and interpreting the data our current methods are already creating.”

Testing Is Only the Beginning

Due to advances made in genomics over the past several years, the physical risks from genetic testing have been greatly minimized. Even among expectant mothers over 35, for whom amniocentesis or chorionic villus sampling tests are often recommended and are associated with an increased risk of miscarriage, minimally invasive blood tests are being developed that are able to detect fetal DNA from the maternal sample, providing many of the same results as the invasive procedures.

Yet, genetic testing often comes with its own unique set of limitations and concerns, especially when viewed through the lens of neurologic disorders. Often physicians wrestle with the limited predictive value of genetic tests for diseases that basic science researchers are still grappling to fully understand.

The quintessential example of the dichotomy between whether an individual should be tested or not resides within the neurodegenerative condition known as Huntington’s disease (HD). It is an autosomal dominant disorder that contains a mutation in at least one copy of the Huntingtin gene. Due to the inherited nature of HD and its typically late age onset, testing for the Huntingtin mutation can be done at any age during an individual’s development, well in advance of any physical symptoms.

Obviously, this raises several key concerns that are still the subject of active debate. For example, should genetic information be obtained from an individual if no treatment or intervention options exist? This dilemma had been debated for many years because, until recently, treatment options were almost nonexistent. While currently there is still no cure for HD, treatments for managing patient symptoms have vastly improved. Additionally, since HD can be tested for at a young age, an ethical quandary is raised as to what is the appropriate age considered mature enough to choose testing options and do parents have the right to have their children genetically tested for a disease that won’t manifest itself until well after they have reached adulthood?

Where the ethical discussion ends is often the starting point of legal arguments. Who owns the data from a genetic test? Can test data be used by insurance companies or law enforcement for predictive/presumptive purposes? Legitimate questions that represent real scenarios that are possible in the world are becoming increasingly reliant on technology and metadata.

Another interesting question and thought scenario comes when viewing the current political climate in the U.S. Will neurologic genetic tests be a requirement in the future for gun ownership or to run for public office? Imagine in 1984 that there had been a genetic screen available to suggest that in five years’ time Ronald Reagan was highly likely to develop Alzheimer’s disease. Would the American electorate still vote for him a second time?

Lastly, the ethical and legal arguments notwithstanding, the science surrounding many genetic disease tests is always in a state of constant flux. Good science takes time and reproducibility for it to be accepted as true. Whether a set of biomarkers is an accurate predictor for disease is reliant upon solid research data, often difficult to come by for various reasons, the least of which being the scarcity of clinical studies.

“Genetic diseases by their nature are rare. This makes getting adequate numbers of impacted individuals to do well-controlled studies one of the biggest obstacles,” says Kim Caple, SVP of clinical business for Affymetrix. A fact that is certainly valid for neurologic disorders with genetic components, which have some of the lowest incidence rates in comparison to other genetic diseases of the body—Alzheimer’s disease being a noted exception.

“There are numerous challenges, but among the greatest are developing tests that are deemed to have clinical utility that will impact medical management,” added Dr. Friez. “And once that criteria is addressed it takes time to convince insurance providers that the testing should be reimbursed.”

Future of the Mind Is What Matters

Ethical concerns and test limitations will always be an ingrained part of the genetic testing process. As scientists we can only hope to make discoveries that will advance our respective field forward, keeping the number of ethical quandaries to a minimum. Improvements in new technology are poised to make genetic disease testing more accurate, faster, and lest costly. “The genetic testing field will continue to progress in diagnostic yield with use of both chromosomal microarrays and next-generation sequencing,” Caple states.

Additionally, the number of screenable biomarkers for neurologic disorders containing genetic mutations has surged since the introduction of NGS sequencing techniques about 10 years ago. Genetic panels can be broken into subsets such as epilepsy and neurodevelopmental disorders, neuromuscular diseases such as Duchenne muscular dystrophy, and neurometabolic diseases such as Tay-Sachs and Fabry disease.

Consequently, there are a host of other neurological disorders with genetic components that aren’t as easily characterized for which biomarker panels exist—Fragile X syndrome, congenital insensitivity to pain, and some of the most recent genes associated with autism.

The real power of precision medicine will blossom into its full potential when genetic testing panels are combined with data from pharmacogenomic screens. A scenario that should allow physicians to pick the most effective treatment options based on the results of the neurologic genetic test. Identifying the genetic profile for a neurologic disorder is only truly useful if the polymorphisms that would eliminate various ineffective therapeutic regimens are recognized. Disease morbidity is sure to decrease while simultaneously increasing treatment efficacy if clinical research flows along that path.

Finally, genome-wide association studies have begun to comparatively analyze patient DNA from clinically distinct neurological disorders. The hope is to uncover a pathological overlap that would reveal a biological link between disorders and their more encompassing disease traits, such as neurodegeneration. These studies are ultimately designed to determine if different diseases share a common genetic risk. But no commonalty has been discovered to date.

“To partner with all this data will be improved tools to manage and interpret the data,” Dr. Friez stated. “We will need to become more nimble in our ability to leverage increasing volumes of data into better and more meaningful medical care.”

In the end, the brain still remains an elusive territory where genomic research is just beginning to navigate. However, in just a short period of time new discoveries and mass quantities of data are piling up exponentially. The mental tipping point is on the horizon.


This article was originally published in the August 2015 issue of Clinical OMICs. For more content like this and details on how to get a free subscription to this digital publication, go to

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