Science. That provides new insights into the causes of ALS. She discusses the research findings and explains why discovering just one new gene can make a big difference.">

Feb 27, 2015 — In the wake of the ALS ice bucket challenge, scientists have made important progress on discovering causes of amyotrophic lateral sclerosis also known as Lou Gehrig’s disease. Summer Gibson, M.D., co-runs the ALS clinic at the Clinical Neurosciences Center at the University of Utah and is an author on a paper in the journal Science Science. That provides new insights into the causes of ALS. She discusses the research findings and explains why discovering just one new gene can make a big difference.

Interview

Interviewer: New insights into the causes of the ALS, up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs. The Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Summer Gibson who co-runs the ALS clinic at the Clinical Nerosciences Center at the University of Utah. She's an author on a paper in the Journal of Science that reveals new insights into the genetics of ALS. I think first before we go into the research results, it's important to understand there are different kinds of ALS. What are two of the main categories?

Dr. Gibson: If you were to define them as two main categories then you would say that there is familial ALS or, those that report a family history of ALS. That's anyone who says that either they have a mother, brother, sibling, grandparent, or child that has had ALS. Then there's another group that we call sporadic ALS. Although, as we're identifying more and more genes we're realizing that those things are somewhat as not as useful of categories as we originally thought.

Interviewer: Now why is that?

Dr. Gibson: Because we're actually finding that some genes that cause ALS can cause other types of neurological disorders like frontal temporal dementia.

Interviewer: Okay.

Dr. Gibson: So you may find a family in which there has been people that have had frontal temporal dementia for several generations and that history of having ALS is sort of lost. So I think that those categories have been in theory very useful, but I think they're starting to blend more and more.

Interviewer: Okay, so you mean things that you once thought were spontaneous may also be familial.

Dr. Gibson: That's correct, yeah.

Interviewer: Okay, interesting.

Dr. Gibson: So we used to think the rate of familial ALS was about 5% and that about only about 5% of ALS was related to genes, but we're discovering each day that that's not correct and each day it seems like we're adding something new to the list and percentage.

Interviewer: Okay, interesting. So what was it that you found in this particular research?

Dr. Gibson: In this research we found one new gene that has never been identified before. This was a very large collaborative effort. It involved people that had no reported family history of ALS, so the group that we call sporadic ALS. The new gene that we discovered is TBK1, and that is quite a mouthful, that is now gene number 18 that is causative for ALS.

Interviewer: So what's special about this gene? Why was this an important finding?

Dr. Gibson: Right, yeah. So I think that many people may think that this is just one of many kind of thing. The reason that it's so important is that we're finally starting to see the genes cluster in groups and have similar pathways. And so when you find one gene if you find a second gene that seems to have nothing in common then that's less important. But what we're finding is the genes are now starting to cluster together and we're finding common pathways that are involved in causing ALS. So I think that's the reason it's so important, is the pathway discovery.

Interviewer: So maybe you can talk more about the pathway. So one thing that I think you were saying is that this gene works with other genes or the products of those genes to regulate one biological phenomenon. So what is that? What pathway are you talking about?

Dr. Gibson: So the pathways I'm talking about, autophagy is the main category, it also falls into the innate immunity. So that's the immune system that doesn't have anything to do with getting a virus or an infection or a vaccine, but is something more like skin or some barriers that we have that are sort of our first defenses. Then autophagy is sort of the cells way of getting debris.

Interviewer: So if you're talking about autophagy for example, the idea I imagine what you think is happening is that there's just a lot of trash that's accumulating in these cells and this is contributing to the problems that are part of ALS.

Dr. Gibson: Exactly. Yeah and we think that the motor neurons which are affected in ALS, both the upper and the lower, are probably more sensitive to those cellular debris and the build of cellular debris. So that may be why these cells are affected and not other cells in our body.

Interviewer: So TBK1 is involved in both these pathways but you also know that other genes that have been linked to ALS are also part of these pathways and that's the important part, right?

Dr. Gibson: Exactly and I think that even those genes that have been discovered like C9orf72 which is an expansion gene, we're thinking the most common recent thought is that the reason that it's pathological is that protein itself, when it has that elongated mutation and causes the protein to clump and then to aggregate and cause problems within the cell.

Interviewer: And become part of that trash?

Dr. Gibson: Exactly. So we're seeing the trash from some of the proteins. Then we're also seeing that proteins that are supposed to be involved in removing the trash are involved. So I think things are actually coming together, which is really an exciting turn. I think it's really starting to finally illuminate a pathway that hopefully can be really transnational.

Interviewer: How are you continuing this research?

Dr. Gibson: So, this is just one step. I think until we've discovered all the genes out there and fully explored the pathways involved, it's only a small step in that direction and hopefully as we discover more we're certainly going to create more interest from drug companies to then want to be involved. I think when you don't understand if a disease is one disease or many diseases, you don't understand the mechanisms, it's just somewhat of a Pandora's Box for a drug company to really approach it. So I think these are some of the key features that we have to have before we get more investigation in those areas.

Interviewer: Is there anything else you would like to get out there?

Dr. Gibson: I know that there was a lot of pessimism that followed the ice bucket challenge. At least in the final stages when people were starting to get bored of seeing it. What I really wanted to remind people is that it is a really challenging disease. This brings incredible challenge for patients, for families, and for those that love and care for those patients. I think it's one of those disease that nightmares are sort of made from, also my patients are really. . . I'm always amazed and impressed and reinvigorated by their zest for life and just the grace that they come through this disease with.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope, Health Sciences Radio.