DESLEY BLANCH : A new treatment to stop the progress of Alzheimer's disease moves closer after a research breakthrough by a team from the University of Sydney in New South Wales.
At the university's Brain and Mind Research Institute, Professor Juergen Goetz and Dr Lars Ittner and their colleagues claim they have isolated the cause of the brain-wasting disease after their study showed how two key proteins interact in an otherwise healthy brain cell to trigger the disease.
Juergen Goetz and Lars Ittner talk to us from our ABC studios in Sydney.
DESLEY BLANCH : Alzheimer's is a disease predicted to affect one in 85 people globally by 2050 making it a major health threat to the world's ageing population and with an associated enormous toll taken on families and caretakers, so what are the current treatments? Juergen Goetz.
PROFESSOR JUERGEN GoeTZ : Yeah unfortunately, there is no cure from Alzheimer's disease and that holds true for Alzheimer's disease and also a lot of related dementias. There are basically only a handful of treatments which is available.
DESLEY BLANCH : Well Lars, you believe you have isolated the cause of the brain-wasting disease, Alzheimer's, so what have you found?
DR LARS ITTNER : Well, what we've actually found is like how the two main proteins that are known for about 100 years now to be deposited in the brain of Alzheimer's patients; we found the way they interact with each other and that's by interacting with a third protein which then sensitises the neurons for toxicity caused by the amyloid beta protein.
DESLEY BLANCH : Well Juergen, your job as a researcher is to understand the basic mechanisms underlying these disorders and in 2001, you figured out that these two proteins, amyloid-beta and TAU did act together in disease and now you've learned their connection. So what is their relationship to one another?
PROFESSOR JUERGEN GoeTZ : Yeah in 2001, we published a paper in a major journal, Science, showing that amyloid-beta which is outside of a nerve cell can exacerbate a TAU pathology. TAU is an intraneuronal protein and we showed that when we injected Abeta into a brain this caused a more pronounced TAU pathology, and this is known in the field as the amyloid cascade hypothesis because it places amyloid upstream of TAU.
DESLEY BLANCH : Well Lars, your findings challenge the current set of concepts accepted by current research, but you've gone on to explore the potential of your discovery in looking for a treatment of the disease. What did you do in your mouse model?
DR LARS ITTNER : At the starting point, when we started actually this work was that the TAU protein that Juergen just referred to is in one process of a neuron called Axon while the other player in Alzheimer's disease, the amyloid-beta protein acts on the dendrite which is virtually the other end of a neuron and so it didn't make sense how these two proteins should talk to each other.
And what we actually did is that we shortened TAU and expressed that and introduced it genetically into mice and that enabled us to identify certain proportion of the TAU protein which is actually in the dendrites and that's the spot where the amyloid-beta protein acts toxic on neurons.
DESLEY BLANCH : And did any of the treated mice die or suffer memory loss or have seizures?
DR LARS ITTNER : We used mice that were genetically engineered to develop Alzheimer's, so we did this by using a mouse strain which expresses mutations which are found in rare familial cases of Alzheimer's disease and this mouse strain was characterised by memory loss and also by seizures and by early lethality, so mice die really early. And by treating them, we were able to reverse memory loss and also rescue these mice from seizures and we also showed a normal life span which was really remarkable.
DESLEY BLANCH : So they actually reversed memory loss?
PROFESSOR JUERGEN GoeTZ : That's correct yeah. We could reverse memory loss. I mean, we did the treatment at an early age, and as the mice aged they would have developed Alzheimer's but that was not happening and the surprising thing was that we could rescue memory loss despite the fact that this toxic peptide the amyloid peptide was still hanging around, so it could not, as Lars has said, it could not exert its toxicity anymore, because of our treatment.
DESLEY BLANCH : And how did you give the protein to the mice?
DR LARS ITTNER : We used an approach that is very common in our field and that is you can use little pumps. They are a kind of asthmatic —like insulin pumps in diabetic patients but way smaller, and with those we can infuse the protein directly into the brain of mice.
DESLEY BLANCH : Well Juergen, it's taken you both five years to reach this point. So why is your discovery such a significant breakthrough?
PROFESSOR JUERGEN GoeTZ : It's essentially a goal that the amyloid plaques and the TAU tangles have been identified by Alois Alzheimer, I mean it was really for a long time not known how this deadly amyloid-beta exerts its toxic effects. And this paper shows how it does exert it, that TAU is involved in basically mediating the toxic effects and from a scientific point it's a real breakthrough. but it also opens new areas for treatment.
DESLEY BLANCH : Well Lars, are any of the pharmaceutical companies coming to you with a desire to develop ways of administering the treatment for humans? Or do you at this point approach them?
DR LARS ITTNER : We have actually a year ago roughly patented our findings and in the course of this year approached pharmaceutical company, one which is really interested in our work to develop screening essays that would allow identifying then small compounds that could interfere with the mechanism that we have identified.
I just came back from Hawaii, where we've actually presented our findings for the first time and in the audience were quite a few representatives of pharmaceutical companies, mainly from the United States and we had afterwards some really good discussions about possibilities to explore our findings.
DESLEY BLANCH : Well Juergen, because your approach targets the underlying biology of the disease and not the symptoms - is this a reason for you to hope for a treatment available sooner rather than later?
PROFESSOR JUERGEN GoeTZ : I would say so yes. The pharmaceutical industry pursues a lot of strategies at the moment and we sincerely hope that any of these treatments will lead to a patent within a reasonable time frame and as far as our approach is concerned, I mean it may take awhile, but I mean we are very dedicated to develop a compound based on our findings and it's difficult to predict at the moment how long this will take.
DESLEY BLANCH : Well Lars, do you have any ideas on why some people are susceptible to this disease and contract it?
DR LARS ITTNER : There's certainly a population amongst the patients with Alzheimer's disease which have a genetic risk meaning they have mutations in certain genes that are linked to Alzheimer's disease like the APP (Amyloid Precursor Protein) chain itself or they carry certain risk genes like the Apoe4. But one has to say that the majority of Alzheimer's disease cases it is not actually known what is the cause.
DESLEY BLANCH : And Juergen, what brought you to this research? Was there a personal connection with the disease which started you on this path?
PROFESSOR JUERGEN GoeTZ : I spent all of my life in academic environment, except for three years when a did a post-doc in industry, that was in Basel in Switzerland working at Novartis in the pre-clinical research department and that was where I first got in touch with Alzheimer's research and that was also where we developed the first animal model for the TAU pathology for Alzheimer's disease.
But on the other hand, as you say, there are a lot of relatives also parents of friends and school mates with whom I am in touch and these parents, a lot of them have Alzheimer's disease. When I look back maybe 20 years, I have not heard of this disease, but now, to whom ever I talk, I mean there are Alzheimer's cases in the family and even in my family on my mother's side, my grandmother she is 85 years old and she has Alzheimer's since two years and it is very horrible to see that.
DESLEY BLANCH : And that's not senile dementia, this is separate isn't it?
PROFESSOR JUERGEN GoeTZ : Senile dementia: there is pre-senile dementia and dementia. There is no real line drawn between the two. Pre-senile means simply that you have genetic cases as Lars has just referred to, with mutations in the genes, which encode the proteins which are deposited in the Alzheimer's brain and in these cases you can have the onset of dementia even at an age of 30 years, which is remarkably early.
DESLEY BLANCH : Very young.
PROFESSOR JUERGEN GoeTZ : That's very young, but when you look at the clinical features or at the changes in the brains -- the histopathological changes, then there is no difference between what has been previously known as pre-senile and senile dementia. So they are similar, only that in one case you have an earlier age of onset, a very early age of onset -- before the age of 65 or 70.
DESLEY BLANCH : Well Lars, what's been the reaction from the scientific community to your research?
DR LARS ITTNER : As I said before, when we presented the findings at International Alzheimer's Conference in Hawaii, we had a very good response after the talk, we had really long discussions until actually late at night about our work and also we received a lot of feedback from our colleagues, reaching from congratulations up to questions on our work and also there is a platform which is called The Alzheimer Forum and there, colleagues can place scientific comments on our work and for our tests and throughout been very positive. And maybe I also have to receive quite a lot of response from patients or mainly actually from their relatives asking directly for progress.
DESLEY BLANCH : And on that very point, what is your immediate next step for you both?
PROFESSOR JUERGEN GoeTZ : There's obviously scientifically we want to learn more about how Abeta interacts with TAU, so we've mentioned these two proteins which interact and then disrupt this interaction.
We have a treatment and so from a scientific point of view we want to understand more how these proteins interact and then obviously we would also like as Lars has mentioned, we would like to develop a treatment starting with a peptide.
Based on this peptide we would like to model some more compounds which we would then test in cell culture and in vitro systems and eventually enemas and hopefully at some point also in humans in clinical trials and so we hope that our work contributes to finding a treatment and a cure for Alzheimer's disease.
DESLEY BLANCH : Five years a good time frame?
PROFESSOR JUERGEN GoeTZ : (laughs) You're not the first one to ask this question.
DESLEY BLANCH : We're all waiting.
PROFESSOR JUERGEN GoeTZ : Someone mentioned five years at some point, so it took us five years to come up with these findings and this has been interpreted as it takes five years to develop a treatment.
DESLEY BLANCH : Exactly, five years.
PROFESSOR JUERGEN GoeTZ : Yeah, I see. Five years, let's put it this way five to ten years. I think it takes two years to come with good compounds and then one has to go through different clinical phases. I mean, collaborating with industry I know how long it takes having worked in industry myself. So I think five to ten years, but more generally I hope that within five years there will be a treatment for Alzheimer's disease, if not based on our approach.
DESLEY BLANCH : Professor Juergen Goetz and Dr Lars Ittner are from the Brain and Mind Research Institute at the University of Sydney where they've identified at a cellular level what causes Alzheimer's disease, thus opening doors for the development of possible therapies.
DESLEY BLANCH : Now to that mobile invention that could be a desert life line.
Alzheimer's brain on Left