Incurable Nervous Disease The most common genetic factor identified for ALS

Nervous disease: So far most common genetic factor of familial ALS discovered

The rare nerve disease Amyotrophic Lateral Sclerosis (ALS) has been known to many people since the so-called "Ice Bucket Challenge". Thousands of people around the world poured ice water over their heads to raise money for ALS research. Researchers have now identified the most common genetic factor of familial ALS.

Incurable nerve disease

The neurodegenerative disease ALS, which can lead to violent muscle twitching and heavy swallowing problems among other things, leads to the destruction of the motor nerve cells and thus to steadily progressive paralysis. The relatively rare disease - about three out of every 100,000 people are affected each year - is not yet curable. Although ALS has gained popularity with prominent patients such as physics professor Stephen Hawking and the "Ice Bucket Challenge" in the summer of 2014, treatment remains difficult, especially as the true causes have not yet been identified. But researchers have now discovered the most common genetic factor of familial ALS.

The Incurable Nervous Disease Amyotrophic Lateral Sclerosis (ALS) has been known to many people since the so-called "Ice Bucket Challenge". Researchers have now identified the most common genetic factor of familial ALS. (Image: Iliana Mihaleva / fotolia.com)

Interplay of several genetic defects

Ulm University researchers have discovered mutations in the KIF5A gene that can trigger the hereditary variant of the neurodegenerative disease amyotrophic lateral sclerosis (ALS).

According to a communication, this is the genetic factor that has so far been most frequently detected in patients, which contributes to the development of ALS.

The study, published in the renowned journal "Brain", further supports the assumption that the deadly disease is based on an interaction of several genetic defects.

Illness leads to death within a few years

As a rule, the complex and currently incurable neurodegenerative disease causes ALS to die within three to five years after the onset of the disease.

The sporadic variant is differentiated from the hereditary ("familial") form, which accounts for only about ten percent of the diseases. In both cases, the disease is not yet understood exactly.

However, thanks to recent advances in DNA sequencing technology, scientists have been able to identify several genes whose mutation is a predisposition to ALS.

However, these mutations only explain the cause of less than 25 percent of all cases.

At the onset of the disease several gene changes seem to work together

Now, researchers from the Ulm University Department of Neurology (Rehabilitation and University Clinics Ulm) and the University of Umeå Sweden compared the genome of 426 ALS patients who had at least one other diseased relatives with a healthy control group (so-called "total exome sequencing ").

The scientists led by Professor Jochen Weishaupt and Professor Peter Andersen have identified three so-called splice site mutations in ALS patients in the C-terminal domain of the gene KIF5A, which lead to a loss of function of the corresponding gene.

In three studied families, the inheritance of the disease was linked to such a mutation over several generations.

In addition, in several patients with familial ALS, the authors found an accumulation of single nucleotide polymorphism (SNP) rs113247976, which also affects the KIF5A gene.

"In six percent of familial ALS patients we were able to detect this polymorphism and again 50 percent of them had at least one mutation in another known ALS gene. This indicates that many genetic defects often interact in disease transmission, "explain Professor Weishaupt and first author Dr. Ing. David Brenner.

Of all the genetic changes found in ALS patients worldwide since 1993, rs113247976 is the most abundant genetic factor contributing to the disease.

Also, other neurological disorders associated with the affected gene

The KIF5A gene is the blueprint for a protein involved in the transport of substances in the axon of a nerve cell. The study results underscore the importance of intracellular transport processes in ALS disease development.

In addition, other neurological disorders are associated with different changes in the KIF5A gene (hereditary spastic paraplegia, Charcot-Marie-Tooth disease type 2, neonatal intractable myoclonus).

In the future, the newly published findings could contribute to new molecular therapies.

"In summary, this study adds KIF5A to a growing list of genes that cause ALS, and it extends the spectrum of mutations in this gene," emphasizes Professor Albert Ludolph, medical director of Ulm University's Department of Neurology.

The high prevalence of the SNP KIF5A rs113247976 in familial ALS patients also fueled the hypothesis of a combination of different gene defects in a patient. This could also genetically explain some of the sporadic, non-familial ALS cases.

New insights into the causes of ALS

Other researchers have gained important insights into the causes of ALS in recent years.

For example, Australian scientists have found new gene variants that contribute to the disease in many cases.

According to a report published on the ScienceDaily portal, Professor Naomi Wray of the University of Queensland said: "These three new genes open up new research opportunities to understand a complex and debilitating disease that is currently under attack no effective treatment yet. "

The study results of Dutch researchers are also interesting. As the experts from the Utrecht University in the journal "Occupational & Environmental Medicine" reported, apparently also electromagnetic fields ALS trigger. (Ad)