Norman Swan: Alzheimer's disease is the commonest form of dementia, and the results of billions of dollars of research investment have been bitterly disappointing in terms of finding an effective treatment. However, experiments on mice by a group from the Dementia Research Centre at Macquarie University have come up with some promising findings. Professor Lars Ittner is the director of the centre. Welcome to the Health Report Lars.

Lars Ittner: Hello, how are you?

Norman Swan: Now, essentially you are targeting an enzyme which protects nerve cells in the brain from the toxic effects of amyloid beta and that's one of the two main substances which accumulate in Alzheimer's disease. What did you actually do in this study?

Lars Ittner: So in this we found prior to this study that this enzyme activity that protects the brain from Alzheimer's disease is actually lost in Alzheimer's disease. And we devised a gene therapy to replace the enzyme activity and bring the enzyme back into the brain cells.

Norman Swan: And these are mice which replicate Alzheimer's disease in some shape or form.

Lars Ittner: Yes, they are, so we genetically engineered them to develop Alzheimer's disease.

Norman Swan: And they were showing signs of memory and thinking problems?

Lars Ittner: Yes, so their ability to form memory and then store the memory over longer terms is compromised.

Norman Swan: And this was the gene for this enzyme?

Lars Ittner: So we brought backit's called the P38 gamma gene, which we brought back into the brains of these mice and that restored their ability to form memory.

Norman Swan: So you actually got healing?

Lars Ittner: So we were quite surprised because when you set out with these type of studies you expect at most that you stop the progression. But yes, we got far more than we set out for.

Norman Swan: People have tried gene therapy before from Parkinson's disease and other things, and it's quite hard to get the gene therapy into the brain. And of course Alzheimer's disease is quite widespread as opposed to Parkinson's disease. How do you get the gene therapy in reliably?

Lars Ittner: So from the early days of gene therapy done in Parkinson's disease, the vehicles that are used to bring the genes into organisms or in the brain in particular have improved, so these days we use modified viruses that we take advantage of their ability to infect brain cells, and they then deliver the genes for us.

Norman Swan: In the right place. Were there any side effects?

Lars Ittner: So we did toxicity studies as part of our study, and then you use incredibly high amounts of the virus, and we did not see long-term side-effects.

Norman Swan: How do you getthere's something called the bloodbrain barrier, the brain is a protected organ and it's quite hard for things to get into the brain because of this barrier, how did you get beyond that with these gene therapies?

Lars Ittner: So with the mice we can take advantage of a modified virus which has been selected to actually passage this naturally, but in humans you would do a single injection, it's like a lumbar puncture, it's at the base of your neck, and it's directly into the liquid around the brain, so you basically mechanically bypass the bloodbrain barrier.

Norman Swan: There have been very disappointing results. I mean, what happens in mice particularly in Alzheimer's disease does not necessarily happen in humans, and there's not a single amyloid beta therapy that has had much effect on the brains of the people with Alzheimer's disease. Why do you think this one might work in humans when others haven't?

Lars Ittner: So the problem with the amyloid beta is that it is now understood that this is a disease inducing pathology but is not required for the progression of the disease, and we are targeting here actually the tau protein specifically which is

Norman Swan: It's the other thing that

Lars Ittner: Exactly, and that is responsible for the progression of the disease, so it's actually moving away from the amyloid beta as a drug target which has failed in the past.

Norman Swan: Now, with COVID-19 around we are getting used to the language of clinical trials and accelerating trials. When are you ready to go to phase 1 which would be a safety trial in humans?

Lars Ittner: So preclinical experiments have actually been completed for this particular study, and the next step are in fact phase 1 clinical trials, and we are currently working with Macquarie University and their commercialisation arm to find the right partner to move forward into clinical trials.

Norman Swan: Fascinating. Well, we'll follow that up when you do. Thanks for joining us.

Lars Ittner: It was my pleasure.

Norman Swan: Professor Lars Ittner is director of the Dementia Research Centre at Macquarie University.

You've been listening to the Health Report, I'm Norman Swan, and I'd really enjoy your company next week.

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Of mice and memories: Gene therapy study returns function in Alzheimer's mice - ABC News