ELIZABETH FARNSWORTH: Next, new research about Huntington's Disease. Three new studies published in the journals "Cell" and "Neuron" show that excess protein formulation in the brain appears to be responsible for Huntington's Disease and six other similar debilitating neurological disorders.
To explain, we're joined now by Dr. Christopher Ross, director of the Huntington's Disease Research Center at the Johns Hopkins School of Medicine. He was also a co-author of one of the studies released today. Thank you very much for being with us, Dr. Ross. What is Huntington's Disease?
DR. CHRISTOPHER ROSS, Johns Hopkins School of Medicine: Huntington's Disease is an inherited neuro-degenerative disorder in which patients lose control of their ability to think and to move and slowly go downhill and eventually die of the disease. It's a very tragic disorder.
And it's a disorder which is inherited genetically within families. Anyone who's affected with the disorder has a 50 percent chance of passing it on to any of their children. And it generally begins in adult life. So, often they don't even know that they're going to get the disorder before they have children, and, therefore, it continues to progress in families.
ELIZABETH FARNSWORTH: And it's not treatable, right?
DR. CHRISTOPHER ROSS: So far, there are no treatments that can slow the effect of the illness. Usually, people die within fifteen to twenty years of getting their first symptoms.
ELIZABETH FARNSWORTH: Now, you knew--it was discovered four years ago that a certain gene played a role in it, right? So what's happened that's changed what's new about these studies?
DR. CHRISTOPHER ROSS: That's right. So after really a long search to find the Huntington's Disease gene, it was discovered four years ago in a collaborative study, and that was a big breakthrough, but the unfortunate thing was the protein that the gene made had no resemblance to any other known protein, and, therefore, no clear function within the cells. And so we didn't know either what the normal function was, or what it might be doing to damage the brain and kill nerve cells, which is what the effects of the disease are.
ELIZABETH FARNSWORTH: And your study found-
DR. CHRISTOPHER ROSS: Our study, we believe, gives us a very strong lead as to what the protein does to actually kill nerve cells. And I could show-
ELIZABETH FARNSWORTH: Please do.
DR. CHRISTOPHER ROSS: Here in the brain, the area of the brain that's affected in HD. This is a model--
ELIZABETH FARNSWORTH: HD being Huntington's Disease-
DR. CHRISTOPHER ROSS: --of Huntington's Disease, right. This is a model of the brain showing the--what's so called the cortex, the place where we do all our thinking and control of movements. And then if I turn the brain around, you see on the inside a region called the basal ganglia. And this is the region that's most severely affected in Huntington's Disease.
And what happens is for reasons that have so far been unclear, nerve cells within this region--both in the cerebral cortex and in this region called the basal ganglia--simply begin to die, so that patients lose control of their bodily functions. And if we were to take a cross-section through a brain of an actual patient with Huntington's Disease, as shown in the picture that we have-
ELIZABETH FARNSWORTH: Oh, yes. We have a couple of pictures here too.
DR. CHRISTOPHER ROSS: So this picture shows these are postmortem brains from a normal individual and an individual with Huntington's Disease. They're actually turned on their side compared to the model. But you can see that the brain from a Huntington's Disease patient is overall shrunken and smaller.
And, in particular, the region in the center of the brain is severely shrunken. In fact, you can see the enlargement of the black area, the fluid-filled space within the brain, due to the shrinkage of the brain caused by loss of neurons, loss of the cells of the brain.
ELIZABETH FARNSWORTH: And is the significance of the studies released today, of which you were one of--you participated in one--that you know now why that happens?
DR. CHRISTOPHER ROSS: Well, it certainly gives a strong clue as to why cells die. I think it's a little premature to say we know for sure. But what we found is that the Huntington's Disease protein--that is, the protein made by the DNA in the HD gene--the Huntington's Disease protein abnormally changes its location within the cell, and it accumulates in kind of a dense mass that we hypothesize gums up how nerve cells work. And this is due to the chemical change in the protein caused by the mutation in the HD gene.
ELIZABETH FARNSWORTH: Do you know why the gene mutates?
DR. CHRISTOPHER ROSS: That was discovered as part of the discovery of the HD gene four years ago. This is a kind of mutation called an expanding triplet repeat mutation, which is becoming increasingly common and seen in more and more diseases, especially in neuro-degenerative diseases.
ELIZABETH FARNSWORTH: Like, for example, just before we go on-
DR. CHRISTOPHER ROSS: Like Huntington's Disease is a member of a class of diseases which include spina cerebellar ataxia, three different forms of it, a disease called DRPLA, which is a rare inherited disease, and a disease called SPNA, which is another rare inherited disease. But all of them were caused by the same kind of genetic mutation, an expanding triplet repeat.
And what's exciting about this finding in Huntington's Disease is that it gives us strong clues about how all these diseases work. And in one of the other papers being published later this month, the one that you mentioned in "Neuron," it was found that the same kind of changes that we observe in the Huntington's Disease protein take place actually in patients with a related disease, SCA-3.
ELIZABETH FARNSWORTH: And--is Alzheimer's related too?
DR. CHRISTOPHER ROSS: Alzheimer's disease is also a neuro-degenerative disease, but it's not caused by this same kind of genetic mutation. What's striking, though, is that we're finding that this accumulation of protein, which we had never imagined to see in a disease like Huntington's Disease, is very much like the fact that protein accumulates in Alzheimer's Disease, in that case a different protein and in a different location in cells and outside of cells, but it's giving us the idea that all of these are degenerative diseases, and they share more features than we have previously established.
ELIZABETH FARNSWORTH: Will the goal now be to find a way to dissolve these globs of protein that are in the nucleus?
DR. CHRISTOPHER ROSS: Well, there are really a number of things that need to be done. First of all, we need to confirm that this protein is present in all of the diseases with this mutation. We need to really see if this protein is killing the neurons, the accumulation of this protein.
ELIZABETH FARNSWORTH: You have the fact that it's there, but you're not 100 percent sure it's killing them.
DR. CHRISTOPHER ROSS: That's right.
ELIZABETH FARNSWORTH: It has to be completely established.
DR. CHRISTOPHER ROSS: That's right. What we have are a mouse model made in England in Jill Bates's lab in which this protein accumulates and accumulates before the animals show any symptoms. And that's the reason why we believe that the accumulation of the protein has something to do with killing the neurons.
ELIZABETH FARNSWORTH: Just for families of sufferers of Huntington's Disease and for the sufferers, themselves, what do you say to them right now about what their hopes can be?
DR. CHRISTOPHER ROSS: Well, we always have to be careful. When we make these kinds of advances in the lab, we don't want people to believe that all of a sudden we have a new medicine or a new treatment. What this really gives us, we hope, is a better understanding of the disease, a way to look further for exactly what's going wrong, and particularly a way to develop in the lab models to screen treatments.
So we can take now Huntington in a test tube, Huntington in these mice with the abnormal Huntington's gene, and we hope in cells in the lab, and treat them with small molecules that can be used as drugs to try and prevent the accumulation of the protein.
ELIZABETH FARNSWORTH: Oh, well-
DR. CHRISTOPHER ROSS: And that would be the hope for developing treatments.
ELIZABETH FARNSWORTH: Well, thank you, Doctor Ross, very much for being with us. Congratulations on your findings.
DR. CHRISTOPHER ROSS: Thank you.
June 19, 2013
