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The Glasgow Neurosociety
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in association with SI, or Surgical Neurology International, and SI Digital are happy to present
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the abstracts and discussion of the 10th anniversary Glasgow Neurosociety meeting held in November of 2022 in Glasgow, Scotland.
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Hassan Ishmael is president of the Glasgow Neurosociety at that time. He's from the Wolfson School of Medicine at the University of Glasgow in Scotland and the United Kingdom
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Faculty commentators are Likith L. Akhandi, who's the consultant neurosurgeon at the Queen Elizabeth University Hospital in Glasgow
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And Amy Davidson, a neurologist, also at the University of Glasgow, also at the Institute of Infection, Immunity, and Inflammation in Glasgow, Scotland.
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Other Glasgow neuro hosts were Alidith Middleton, Vice President of Glasgow neuro, and Edica Choudhry, another Vice President of Glasgow neuro. Thank you. Who's going to be talking to us about a
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comparison of Alzheimer's disease-indicated drugs on neurons generated from Alzheimer's disease, patient-derived, and just pluripotent stem cells. I'll hand over to yourself now. Thank you for
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your introduction. My name is Mizuki Weta, and I am currently a second year medical student at Newcastle University. So this research was conducted as part of my summer research internship at
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Professor Inoue's group at Kyoto University. Prior to my internship, Professor in the Ulis Group found that bromachrypton had an anti-amyloid beta effect on cortical neurons generated from familial
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Alzheimer's disease patients with mutation in the presentinoline one gene. Since the mechanism of action of bromachrypton was not quite understood, my study aimed to compare the effect of
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bromachrypton and four other Alzheimer's indicated drugs on patients. Patient derived IPSCs using immunofluorous sustaining. So what I first did was to culture IPSCs and differentiate them into
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cortical neurons. Then I introduced five Alzheimer's disease indicated drugs into the neurons. The three drugs beta-separatease inhibitor for semiconductors and JJ are already approved Alzheimer's
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disease drug. I additionally selected erogotamine, which was chosen because it has a similar chemical structure to
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bromachriptin. After the cortical neurons were differentiated, they were staying with 14 different primary antibodies and their images were taken using a fluorescence microscope These 14 primary
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antibodies either did not stay in at all, only staying the cell bodies, only staying the neurons or staying both of them. And there were three primary antibodies that I wanted to focus on, which
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were APH1A, base one and personal in one, which showed different staying in patterns and neurons treated with the drugs So the key finding here is that all proteins with the different staying in
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patterns. patterns are a component of either beta-secretase or gamma-secretase enzyme, which are proteins involved in the cleavage of amyloid precursor protein to form amyloid beta. So I concluded
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that bromocrypton may affect the proteins involved in amyloid beta production similar to some of the already approved drugs. Please let me know if you have any questions about this.
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Excellent. Thank you. That was such a great and eloquent summary of what has really brought, you know, you've done a lot of work there, you know, to somewhere that has it. So to sink lanes,
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that's a short amount of time, you know, is very clever. And so when you were just, when you, you were talking about comparing the drugs in the picture, go to me because it was similar to from
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Krit Team. Did you say any trace, you know, with your, with your theorizing that from Krit Team could be involved in the earlier stages? Did Agotamine have a signal as well, or did it not have,
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you know, did it not feel the same? So in the initial research that was done by Professor Inu is lab, they found, they tried a lot of drugs. And one of the drugs that also showed a similar effect
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with Agotamine, and also in my research, it was thought. I've got to mean, and Brahma Krypton tend to show a similar staining pattern, so I think that my choice that they may have a similar
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structure and they want for similar effect may be supported by the research.
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And with what you've learnt from this, you know, this is, you know, a very good high throughput, very much the kind of study at this, how would you take it forward? So as a clinician, I'm
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always interested in the kind of bench to bedside approach. So what would be your next step? What would you think about going forward? In
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terms of what I understood from here and how that would apply in clinical scenarios, it is that I found that it may be involved in amyloid beta production and we think in terms of the amyloid beta
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hypothesis that it's like the production and the buildup that leads to the clinical manifestations. So if it is actually that the. production is what is being targeted, then it means that we would
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have to detect Alzheimer's early and start this treatment early for it to actually be effective for Alzheimer's disease.
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Do you have any, don't worry, if you don't have an answer to this, but do you have any ways that you, like early detection of Alzheimer's, do you mean like doing kind of PET scans? Or is there a
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kind of a clinical way that you could look for this? Do we have one just now?
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Or is that something we need to think about? How are we going to find these early detections? I don't believe you can answer that question. I don't truly understand all the ways, but I understand
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there's some new ways that they're doing, they're trying to detect it earlier and also find genetic people with dispositions that increases the risk to that might be one way that we could detect this
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early I would like no more about it. really interesting. Yeah, absolutely. Doing a genetic profile, and then you could pick out people at risk using family histories, and then classifying them
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genetically, and then considering drugs like bromachritting. And
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would you have any concerns about bromachritting and the side effects? You know, would you be quite happy to have people on it? Long term? Want me to write anything? I think one of the
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benefits of bromachritting is that it's an already approved drug by the FDA, and already used for things like Parkinson's So there's lots of data that we can use to see who would be more at risk for
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using this drug. So I think that is a great benefit for trying drug style already approved. Absolutely. That's great. Thank you very much for talking through your research. Have you did those
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anything else that you wanted to discuss or?
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One thing I would like to add that is that here. Since I wanted to try many different primary antibodies, each of the samples were quite small. So I would like to expand this by just focusing on
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the primary antibodies that show the different staining pattern and increase the sample size and see whether they just happen to be that way in this time or it's actually something that's replicatable.
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Brilliant, that's good. It's always good to have a thought about how you tweak the research and how to move onto it. So that's a really good thing to be able to do Thank you very much. Thank you.
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Thank you, that was fantastic. And I guess I've got a quick question, what's next I guess for yourself? Are you continuing working this? Are you gonna still stay with the lab and try to take it
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forward? Or what are you up to now? Okay, thank you for your question. I really enjoyed this experience. So I
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got more interested in like doing research and what I'm currently thinking of now is that I learned immunofluorone. since doing it, which is a thing that can be used in many ways. But I'm also
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interested in things like Western blotting
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and things like CRISPR-Cas9. And I'm discussing some summer projects that I can learn some new skills and consider what I would like to do in like masters and future research.
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Excellent. Fantastic. Thank you so much. And that concludes our first panel discussion Hi everyone. We hope you enjoy these presentations.
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