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2023-02-03T00:15:45.5590126Z
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Language: EN.
Segment:1 A first-in-human, gene-silencing treatment for Alzheimer's disease with Catherine Mummery.
CATHERINE MUMMERY: My name's Cath Mummery, and I'm a consulting neurologist working at the Dementia Research Center. I head up clinical trials, so I focus mainly on early phase clinical trials in Alzheimer's disease and in genetic forms of dementia like familial FTD and familial Alzheimer's disease.
Segment:2 What is the Neurogenetic Therapies Programme?.
CATHERINE MUMMERY: So this is a really exciting program. We got a 5 million pound grant from the Sigrid Rausing Trust, and we're going to be able to set up a program that's really unique. It's going to take advantage of the attributes that UCL has, so we have cohorts of patients that are some of the best in the world. We have amazing expertise in genetic therapies and trials already. And we have fantastic preclinical work being done at the Dementia Research Institute and in UCL. We can put those things together and work in collaboration with industry to really facilitate drug discovery right from preclinical work in genetic therapies through to first in man clinical trials. And that's a fantastic thing to be able to do.
Segment:3 What is the first-in-human gene-silencing treatment for Alzheimer's?.
CATHERINE MUMMERY: Gene-silencing is a relatively new methodology. And it's incredibly exciting. It's really revolutionizing medicine, especially in neurodegeneration. And it was a real opportunity to be able to use a gene-silencing treatment in Alzheimer's disease. People think that these are only for genetic diseases, but that's not the case.
CATHERINE MUMMERY: If you know that a genetic abnormality causes an abnormal protein and that abnormal protein is something that accumulates and causes a disease, whether or not that genetic abnormality is there, if you treat for that gene, you reduce the protein. So in Alzheimer's disease, what we have done is used an antisense oligonucleotide which is a synthetic nucleotide that maps onto the message from the gene that produces tau protein.
CATHERINE MUMMERY: Tau protein is a pathology in Alzheimer's disease. And if we can reduce it, hopefully we can reduce the rate of the disease or even prevent it progressing. So we started treating with this gene-silencing treatment against tau in November 17. I dosed the first patient in the world here at Leonard Wolfson Centre, which was incredibly exciting. And so far, we're the highest recruiters in the world.
CATHERINE MUMMERY: We have got through a number of participants with no problems whatsoever. It's been a very safe study, and so far, it's looking really promising.
Segment:4 What are the challenges with clinical translation?.
CATHERINE MUMMERY: So gene-silencing treatments are quite intensive treatment. They need to be given into the spinal fluid at the moment in order to get the drug to penetrate into the brain and have the effect you want. So that is not something that's right for everybody, and also we need to have a way of delivering that that is easier for patients to tolerate. So one of the things we have to work very carefully with pharma to do is work out how we can best deliver that in the simplest way.
CATHERINE MUMMERY: The second challenge is these treatments obviously are not for everybody. Not everyone wants that sort of intensive treatment, so we need to develop clear criteria for how we will ensure the right people get the right drugs.
CATHERINE MUMMERY: And finally being able to deliver these drugs is something that needs a center that has the right capabilities. And at the moment in the UK, there are not many sites that could do that, so we really need to work together as a specialist group and try and ensure that we have the facilities to be able to give these treatments when appropriate.
Segment:5 How do you expect the field to progress in the next 10 years?.
CATHERINE MUMMERY: The world of dementia is really exciting at the moment, and things are progressing very quickly from the point of view of the increased amount of funding, the increased amount of research and resource, and that's going to make a critical difference in terms of the advancements that we make in the next 10 years.
CATHERINE MUMMERY: Where I think we'll be going in terms of trials is that the genetic diseases such as familial Alzheimer's disease are really the gateway to understanding the sporadic diseases. So if we can look at the genetic causes of Alzheimer's disease, we know what causes that disease, if that genetic abnormality-- we know what that genetic abnormality does, for example, it causes processing of an amyloid precursor protein to be incorrect.
CATHERINE MUMMERY: So if we can target that with a genetic therapy in those genetic diseases and show it works, we can then extrapolate that to the non-genetic, much commoner forms of Alzheimer's disease. So the next 10 years, I think we will start to see treatments that are actually making a difference in genetic forms of dementia. And I think then we'll be looking to move those into non-genetic forms of dementia.
CATHERINE MUMMERY:
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