At this year’s American Academy of Neurology annual meeting, held April 15 -21 in Vancouver, Canada, Rosa Rademakers and Bryan Traynor received the 2016 Potamkin Prize for Research in Pick's, Alzheimer's, and Related Diseases. They share the $100,000 award for their studies on the genetics of neurodegenerative disease, most notably their independent discovery of a hexanucleotide expansion in the C9orf72 gene that causes frontotemporal dementia and amyotrophic lateral sclerosis (see Sep 2011 news). This finding ended an intense, five-year hunt for a genetic variant on chromosome 9 that segregates with these diseases. Their work touched off an explosion of interest as scientists raced to uncover how the C9orf72 expansion causes ALS/FTD.

Traynor, who works at the National Institute on Aging in Bethesda, Maryland, has also linked mutations in the Matrin 3, CHCHD10, VCP, and TDP-43 genes to ALS  (see Johnson et al., 2014Oct 2014 news on Johnson et al., 2014Jan 2011 news on Chio et al., 2011Dec 2010 news). 

Rademakers, from the Mayo Clinic in Jacksonville, Florida, was instrumental in deciphering how mutations in the progranulin gene cause FTD (see Nov 2008 conference news on Rademakers et al., 2008). She also identified genetic variants that modulate the effect of the C9orf72 expansion. They include variants in the TMEM106B gene that protect carriers and an expansion in the ataxin 2 gene that seems to disproportionately exacerbate ALS over FTD (see Nov 2014 conference news on van Blitterswijk et al., 2014; Sep 2014 news on van Blitterswijk et al., 2014). 

Both researchers collaborate with cell and molecular biologists to uncover potential pathological roles for C9orf72 repeat RNAs and dipeptides, which could become targets for experimental therapeutics.—Tom Fagan


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News Citations

  1. Corrupt Code: DNA Repeats Are Common Cause for ALS and FTD
  2. Evidence Mounts That Mitochondrial Gene Is Bona Fide ALS, FTD Risk Factor
  3. TDP-43 Turns Itself Off, Inclusions a False Lead
  4. Adding ALS to the Manifestations of VCP Mutations
  5. DC: More MicroRNA Implicated in Dementia
  6. Stream of Genetics Pushes FTD Research Forward
  7. Ataxin 2 Variants Take Aim at Motor Neurons, Not Frontal Cortex

Paper Citations

  1. . Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis. Nat Neurosci. 2014 May;17(5):664-6. Epub 2014 Mar 30 PubMed.
  2. . Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis. Brain. 2014 Dec;137(Pt 12):e311. Epub 2014 Sep 26 PubMed.
  3. . Large proportion of amyotrophic lateral sclerosis cases in Sardinia due to a single founder mutation of the TARDBP gene. Arch Neurol. 2011 May;68(5):594-8. Epub 2011 Jan 10 PubMed.
  4. . Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia. Hum Mol Genet. 2008 Dec 1;17(23):3631-42. PubMed.
  5. . TMEM106B protects C9ORF72 expansion carriers against frontotemporal dementia. Acta Neuropathol. 2014 Mar;127(3):397-406. Epub 2014 Jan 3 PubMed.
  6. . Ataxin-2 as potential disease modifier in C9ORF72 expansion carriers. Neurobiol Aging. 2014 Oct;35(10):2421.e13-7. Epub 2014 May 2 PubMed.

Further Reading