Chilean and U.S. researchers discover key in understanding ALS

Research by the University of Chile and the University of Massachusetts may shed light on the origins of the disease. 

Chilean and American scientists working in collaboration have made an important discovery in the fight against amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease.
ALS is a progressive neurodegenerative disease that attacks the neurons in the brain that control bodily movement such as walking, speaking and handling objects, but leave the brain virtually intact. The disease tends to present in adults during their 50’s and over a ten year period slowly paralyzes the patient to death.
Probably the most famous case of ALS is world-renowned physicist Stephen Hawking, who was diagnosed with the disease at 20 and has continued to live and make important scientific contributions despite being almost completely paralyzed.
An ongoing investigation by Dr. Claudio Hetz of the Millennial Institute of Biomedical Neuroscience at the University of Chile and Dr. Robert Brown of the University of Massachusetts has discovered what they believe to be an important key in unlocking the ALS mystery.
A protein that is responsible for eliminating waste that accumulates in the neurons, known as PDI, may hold the answers that scientists have been seeking. Until now, it was thought that changes in this protein were an effect of the disease, but scientists are rethinking its role. The function of these proteins is “to be chaperones or sentinels that correct changes arising in the structures of other proteins,” Hetz explains. However, sometimes they fail to do their job and as a result other proteins fold incorrectly, causing neurotoxins to accumulate.
Alterations in PDI genes have also been detected in other cerebral diseases such as Alzheimer’s and Parkinson’s disease. However, as Hetz notes, they’ve been “very poorly studied”. The big question that researchers in Chile and the U.S. are now trying to answer is: Why do these proteins fail to do their jobs?
According to Hetz, it’s a domino effect: once one gene mutates all the others begin to fail, creating a kind of pileup—known as protein aggregation—that kills the neuron. To test their hypothesis, researchers introduced a mutated human PDI gene into healthy zebra fish and rats, and as predicted, the animals began to exhibit symptoms of ALS.
The team has presented its findings in several conferences and is expecting to publish the findings in an international scientific journal. Hetz’s team is also working on two other investigations that examine the use of viruses to correct damaged neurons by delivering protective proteins back into them, both of which have been financed by the Muscular Dystrophy Association and the ALS Association.