Media Releases

At last, hope for ALS patients?

July 28, 2014

TORONTO, ON — U of T researchers have found a miss­ing link that helps to explain how ALS, one of the world’s most feared dis­eases, paral­y­ses and ulti­mate­ly kills its vic­tims. The break­through is help­ing them trace a path to a treat­ment or even a cure.

“ALS research has been tak­ing baby steps for decades, but this has recent­ly start­ed chang­ing to giant leaps,” said Karim Mekhail, pro­fes­sor in the Temer­ty Temer­ty Fac­ul­ty of Medicine’s Depart­ment of Lab­o­ra­to­ry Med­i­cine and Patho­bi­ol­o­gy.  “The dis­ease is linked to a large num­ber of genes, and pre­vi­ous­ly, every time some­one stud­ied one of them, it took them off in a dif­fer­ent direc­tion. Nobody could fig­ure out how they were all con­nect­ed.”

Mekhail and his team dis­cov­ered the func­tion of a cru­cial gene called PBP1 or ATAXIN2 that’s often miss­ing in ALS, also known as Lou Gehrig’s Dis­ease.  Learn­ing how this gene func­tions has helped them con­nect a lot of dots.

“This is an extreme­ly impor­tant find­ing that may help us to bet­ter under­stand and tar­get the path­ways involved in neu­rode­gen­er­a­tive dis­ease,” said Lorne Zin­man, pro­fes­sor of med­i­cine at U of T and med­ical direc­tor of the ALS/Neuromuscular Clin­ic at Sun­ny­brook Health Sci­ences Cen­tre. “The next step will be to deter­mine if this find­ing is applic­a­ble to patients with ALS.”

The key lies in a pecu­liar­i­ty of the human genome. It starts with the DNA, the blue­print that con­tains all our genet­ic infor­ma­tion. The DNA pass­es its infor­ma­tion to the RNA, which floats off to make pro­teins that help run our bod­ies. How­ev­er, with­out ATAXIN2, the RNA fails to float away. It becomes glued to the DNA and forms RNA-DNA hybrids, said Mekhail. These hybrids gum up the works and stop oth­er RNA from ful­ly form­ing. Pieces of half-cre­at­ed RNA debris clut­ter the cell, and cause more hybrids.

“We think the debris and hybrids are on the same team in a nev­er-end­ing Olympic relay race,” said Mekhail. “Over time there’s a vicious cycle build­ing up. If we can find a way to dis­rupt that cycle, the­o­ret­i­cal­ly we can con­trol or reverse the dis­ease.”

On that front, Mekhail made a very sur­pris­ing dis­cov­ery: reduc­ing calo­ries to the min­i­mum nec­es­sary amount stops the hybrids from form­ing in cells miss­ing ATAXIN2. He and his team are study­ing whether a sim­ple, non-tox­ic dietary restric­tion could be used with ALS patients, espe­cial­ly in the ear­ly stages or for those at risk of ALS.

Mekhail dis­cov­ered the hybrids and miss­ing genes in yeast cells and his results were pub­lished as the cov­er arti­cle for the July 28 edi­tion of the jour­nal Devel­op­men­tal Cell. Now his team is repli­cat­ing this research on tis­sue from ALS patients – with very encour­ag­ing pre­lim­i­nary results.

“With­in the next decade or two, I think there’s going to be a rev­o­lu­tion in treat­ment for ALS and all kinds of brain dis­ease,” he said. “These hybrids are going to play a role not just in ALS but in a lot of dis­ease.”


For more infor­ma­tion, please con­tact:

Hei­di Singer
Media Rela­tions Spe­cial­ist
Temer­ty Temer­ty Fac­ul­ty of Med­i­cine, Uni­ver­si­ty of Toron­to
Tel: 416–978-5811