A variant version of the gene for a protein known as KIFAP3 has been found to increase survival time in people with sporadic (nonfamilial) ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease) by an average of 14 months.
The findings of John Landers at the University of Massachusetts Medical School in Worcester, with colleagues from institutions around the world, was published online May 18, 2009, in Proceedings of the National Academy of Sciences. MDA supported Orla Hardiman and Simon Cronin at the Royal College of Surgeons in Dublin, Ireland, for this work.
The researchers conducted a "genome-wide association" study, in which they scanned the entire genome (set of genes) of the study participants, looking for any association of gene variants with ALS risk, survival time or other ALS-related factors.
They analyzed the genomes of 1,821 people with sporadic ALS and 2,258 without the disease from the United States and Europe. Included in the analysis was the survival time in 1,014 people who had died of ALS.
The researchers found a single variant, in the gene for KIFAP3 (kinesin family-associated protein 3), that significantly correlated with ALS survival time.
Human chromosomes are found in pairs, and people with ALS who had the survival-enhancing KIFAP3 gene variant on both copies of chromosome 1 survived an average of 14 months longer than people with this variant on only one chromosome 1 or on neither chromosome 1.
None of the variant forms of any genes in this study were significantly associated with ALS risk, site of onset or age of onset.
The variant in the KIFAP3 gene is one that reduces output from the gene, so that less KIFAP3 protein is produced. The investigators say they don't know why having less KIFAP3 protein would prolong survival in ALS, but they believe, based on the normal function of this protein, that its reduction may reduce transport of toxic molecules inside nerve fibers. They note that KIFAP3 levels are increased early in the disease process in mice with an ALS-like disease due to mutated SOD1 genes.
"Few genetic factors that modify ALS survival are reported," the authors write, noting that none have been identified in previous genome-wide association studies in ALS. "The identification of KIFAP3 as a determinant of progression rate of sporadic ALS is therefore promising."
They note that lowering KIFAP3 production or changing the interactions of this protein with other proteins might be worth investigating as an ALS therapy.