Discovery of new ALS gene

Dec 18 2007

The ALS research team at Umea University in Sweden, working with Dutch and Belgian colleagues, has found new connections between mutations in gene DPP6 and contracting the non-hereditary form of ALS. The findings are being published december 16 in Nature Genetics on the Web.

To try to identify pathological genes that are involved in ALS, the research group at Umeå University, in collaboration with Dutch and Belgian scientists, compared DNA samples from 1,767 patients with non-familial ALS (so-called sporadic ALS, SALS) with DNA samples from 1,916 control individuals. This is the world’s most comprehensive ALS study so far. They looked for DNA mutations that only exist in ALS patients, not in controls. After very extensive analyses they found that a DNA mutation in the gene DPP6 strongly correlates with SALS.

The DPP6 gene is on chromosome number 7 and codes for a protein enzyme, a peptidase that regulates the activity of so-called neuropeptides, that is, substances that affect nerve cells. DPP6 is therefore highly interesting as a candidate gene for ALS. Studies are now concentrating on finding disease-associated mutations in the gene. Just how mutations in the DPP6 gene can lead to ALS is unknown today. At present it is not possible to judge whether the discovery will lead to any new treatment for ALS.

The Swedish component of the study was carried out by Associate Professor Peter M. Andersen, molecular geneticist Anna Birve, and research engineer Ann-Charloth Nilsson, all with the Department of Pharmacology and Clinical Neuroscience, Umeå University.

Extensive research on ALS has been pursued at Umeå University since 1992. The objective is to use new knowledge about the mechanisms behind the disease in order to develop therapies for ALS. The main focus is on molecular biological and genetic aspects of the disease and mutations in SOD1 and other genes. Resources (funding, staffing) do not allow any attempted treatment of patients at present.

The research team at Umeå consists of 23 people in four subgroups, directed by Associate Professor Peter Andersen (genetic research), Associate Professor Thomas Brännström (neuropathology), Professor Stefan Marklund (free radicals and cell research), and Associate Professor Henrik Antti (metabolomics).

References: Michael A van Es, Paul WJ van Vught, Hylke M Blauw, Lude Franke, Christiaan GJ Saris, Ludo Van Den Bosch, Sonja W de Jong, Vianney de Jong, Frank Baas, Ruben van 't Slot, Robin Lemmens, Helenius J Schelhaas, Anna Birve, Kristel Sleegers, Christine Van Broeckhoven, Jennifer C Schymick, Bryan J Traynor, John HJ Wokke, Cisca Wijmenga, Wim Robberecht, Peter M Andersen, Jan H Veldink, Roel A Ophoff, & Leonard H. van den Berg:
Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis.