"We thought this was really interesting and neat," said Johns Hopkins neurologist Jeffrey Rothstein, who was not part of the team. Until now, "there have been no validated risk-factor genes in ALS."
The finding links several clues, including a 2006 discovery by Penn researchers that people with ALS build up abnormal deposits of a protein called TDP-43 in their brains.
The hope is that these puzzle pieces will lead to new treatments. Today, doctors can offer little more to patients than they could to Gehrig when the New York Yankees first baseman was diagnosed in 1939.
"One needs to have all the culprits lined up if you're going to go after them with drug discovery," said John Trojanowski, a Penn brain pathologist who, with Virginia Lee, led the team making the TDP-43 finding.
Trojanowski's team found the abnormal protein deposits by analyzing hundreds of autopsies on the brains of people who died from ALS and other neurological disorders.
He said clumps of TDP-43 also appeared in the brains of people who died from Alzheimer's disease and was sometimes seen in head-trauma cases.
The trauma link is intriguing in light of a paper published last week suggesting that Gehrig and other athletes and soldiers may have died from brain injuries rather than ALS. Gehrig had several serious head injuries and was known for playing despite them.
Some suspect that brain injuries might trigger ALS through a pathway involving TDP-43.
Penn geneticist Aaron Gitler approached the problem by exposing yeast cells to TDP-43 and seeing what happened when he genetically modified the yeast.
