Researchers at the University of Pennsylvania School of Medicine and Veterans Affairs in Seattle, WA, have found a number of new mutations in a disease protein called TDP-43, believed to cause amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, and certain types of frontotemporal dementia (FTD).
The study advocates that these mutations might act as potential drug targets for the treatment of these diseases and also a number of other neurodegenerative diseases like Alzheimer's.
"Now we have a direct link between the genetics and the clinical pathology of these diseases. This solves the question of whether TDP-43 is involved in the disease itself or a just a byproduct of it," Lancet quoted Vivianna M. Van Deerlin, MD, PhD, one of the authors of the study.
"Put this all together and it becomes completely convincing that there are mutations in this gene that causes some forms of ALS," said another author of the study.
These mutations indicate that TDP-43 plays a vital role in causing the disease process, as in some cases its accumulation kicks off the disease, while in others it may act as a downstream player in the onset of pathology.
For the study, the researchers conducted a survey on 259 individuals suffering from ALS or ALS combined with FTD and having brains with pathological TDP-43 protein present. They later found out the DNA sequence of the TDP-43 gene, which was later compared to the normal TDP-43 sequence in people lacking these diseases.
"By doing this, we found two families in which a mutation was present and showed that the mutated gene tracked with the disease. Within the same family, all people tested who have the disease carry the mutated form of TDP-43 and it was absent in the unaffected people tested," said Van Deerlin.
In order to look for the same change in people without the disease outside of the families as controls, the researchers tested 747 Caucasian and 380 Chinese elderly people lacking the disease and could not find the mutated form of TDP-43 in any of them.
"What makes our paper completely distinctive is that we have post-mortem brain tissue from some individuals in one of the ALS families. We showed that people with a mutated form of TDP-43 actually have TDP-43 deposited in their brain," said an author of the study.
According to the researchers TDP-43 shows up in a variety of diseases other than ALS and FTD, for example 20 percent of Alzheimer's cases.
The findings of the study are published online in advance of print publication in the upcoming issue of The Lancet Neurology.