Finding among Europeans

It starts with harmless symptoms: Tripping or experiencing some problems holding a pen or handling cutlery. Then, instances of paralysis occur, progressively spreading to more and more groups of muscles. Patients gradually lose control of their hands and arms, find it hard or even impossible to swallow or speak and usually die as a result of respiratory failure.

ALS: There is no known cause

Amyotrophic lateral sclerosis, better known as ALS or in the US as Lou Gehrig's Disease, involves the gradual death of motor neurons, the cells of the motor nervous system. About one to three out of 100,000 people contract the disease each year. The trigger factors of the massive cell death are still little understood and neither is there any effective treatment. The disease most commonly occurs in people between 50 and 70 years of age; astrophysicist Stephen Hawking and painter Jörg Immendorff, who died in May 2007, are two well-known ALS patients.

There is a specific type of ALS that not only affects the motor nervous system; the patients are additionally afflicted by dementia, which is caused by the death of nerve cells in the frontal lobe. There have long been indications that a mutation on human chromosome 9 might be responsible for this type of the disease, but conclusive evidence of this has been lacking.

Characteristic gene disorder

In a large scale international study, scientists have now succeeded in detecting a genetic defect which is responsible for this type of ALS. For this purpose, they examined the genetic material of more than 4,000 patients, comparing it with 8,000 control samples. They found the defect mainly in patients from Europe. In this group, the relevant genetic defect occurs in more than 20 percent of all cases and it can even be found in almost half of the patients with increased familial incidence of the disease. Descendants of European families living in the US also carry this genetic defect frequently.

In about every third patient suffering from a gene-related ALS variant, the researchers spotted a characteristic disorder at a specific location of the C9ORF72 gene. Taking another already known genetic mutation into account, almost 90 percent of all ALS cases with increased familial incidence can now be attributed to genetic causes. These results are reported in the current issue of the scientific journal Neuron.

Basis for therapeutic treatment

"The function of the C9ORF72 gene is still unknown to date. Our finding appears all the more important for understanding nerve cell disorders caused by this genetic defect so as to create a basis for new therapeutic approaches", says Professor Michael Sendtner. However, in his opinion, an effective treatment is still many years away.

Professor Sendtner is head of the Institute for Clinical Neurobiology of the University of Würzburg. The institute has been involved in this research project for several years. "In 2010, we were able to furnish the first indications of the mutation, which now has been clearly identified in this large scale study, using cutting-edge DNA sequencing methods", says Sendtner.

The work of the research team has been confirmed by the findings of a simultaneously published study conducted by the Mayo Clinic in Jacksonville (USA). In this study, the American scientists were able to identify the same disorder as a trigger factor of ALS. Their research is also published in the current issue of Neuron.

“A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked amyotrophic lateral sclerosis-frontotemporal dementia” Alan E. Renton,Bryan J. Traynor et al., Neuron, doi: 10.1016/j.neuron.2011.09.010

Contact person

Prof. Dr. Michael Sendtner, T: +49 (0)931 201 44000, e-mail: sendtner_m@klinik.uni-wuerzburg.de