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Printable Handouts
Navigable Slide Index
- Introduction
- Lecture outline
- Dementia worldwide
- Types of dementia
- Affected areas of the brain
- Neurotransmission
- Acetylcholinesterase inhibition
- Acetylcholinesterase inhibitors
- Donepezil limitations
- Muscarinic receptors
- M1 receptor expression in the hippocampus
- M1 knockout mice
- Muscarinic receptors still present in Alzheimer's
- Muscarinic signalling still present in Alzheimer's
- Xanomeline
- Animal models
- Prion disease
- Prion disease process
- Mouse prion disease
- Hippocampal cholinergic innervation
- Prion disease and memory loss in mice
- Prion disease and neuroinflammation
- Muscarinic receptors in prion disease
- Murine prion disease
- Targeting the M1 muscarinic receptor (Ortho)
- Xanomeline and prion disease
- Xanomeline treatment in mice
- Why did Xanomeline fail?
- Targeting the M1 muscarinic receptor (Allo)
- Selective M1 receptor targeting
- BQCA in disease context
- BQCA in mice
- Alternative M1 selective PAM
- Treatment during disease progression
- Molecule overview
- Range of cholinergic adverse effects
- Chronic treatment potential
- Key points
- Acknowledgements
Topics Covered
- Brief overview of dementia
- Current treatments for Alzheimer’s disease
- Role of muscarinic receptors in learning and memory
- Using prion disease as a model
- Effects of muscarinic receptor drugs on learning and memory deficits in prion disease
- Types of drugs for different stages of Alzheimer’s disease
Links
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Therapeutic Areas:
Talk Citation
Tobin, A.B. (2019, March 28). Novel approaches to treating symptoms and slowing the progress of neurodegenerative diseases [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/JEBH9855.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Andrew B. Tobin has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Novel approaches to treating symptoms and slowing the progress of neurodegenerative diseases
Published on March 28, 2019
42 min
Other Talks in the Series: G Protein-Coupled Receptors (GPCRs) Signaling in Health and Disease
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Andrew Tobin.
I'm at the University of Glasgow at the Center for Translational pharmacology.
I'd like to present to you our work that we've been doing for,
I would say over the last 10 or 20 years,
looking at novel ways of treating
the symptoms and slowing the progression of neurodegenerative disease.
0:21
The structure of this lecture will be around a brief description of
dementia and current treatments that are
aimed really at symptomatic treatments for Alzheimer's disease.
Then, I'll be asking what are
the best disease models in which to study Alzheimer's disease,
and I'll be looking at our work using prion disease and asking
whether the prion disease mimics some of the hallmarks of Alzheimer's disease.
Then, I'm going into asking whether or not we can target
the M1 muscarinic acetylcholine receptors
to restore memory deficits in neurodegeneration.
A key feature, then, of the lecture will be to ask whether or
not we need to tailor the drugs,
particularly targeting the muscarinic receptor for
different stages of Alzheimer's disease,
where we might need different levels of modulation of disease.
Finally, bearing in mind
the adverse responses that many treatments have for Alzheimer's disease,
asking whether we can develop methods by which we can reduce adverse responses,
and therefore, have chronic treatment of disease that will
slow the progression of neurodegenerative disease.
So, that's the outline of the current lecture.
1:31
So, as many of you will know,
the feature of Alzheimer's disease is, of course,
severe neuronal loss, resulting in a terminal disease state-
patients die of Alzheimer's disease in the end.
Alzheimer's disease and dementia are associated with big numbers.
So, as we go through this slide,
you'll see that currently, worldwide 50 million people have dementia.
It's predicted to double every 20 years.
By 2030, there'll be more than 65 million people,
and by 2050 over 115 million people with dementia.
Actually, strangely enough, the biggest growth in dementia
is in the developing countries and countries
outside of Europe and the United States
because that's where the aging population is increasing the most.
So, it's usually is associated with a Western disease,
but that is actually not true.
It's a worldwide problem,
and there are 10 million people with dementia in Europe at the moment.
By 2040, dementia will be second to cancer as a cause of morbidity in the first world.
Among these big numbers,
there is a number that's missing,
and that is that there are currently no drug treatments
that can slow or change the progression of neurodegenerative disease,
so-called modify the disease.
The world and the pharmaceutical industry at the moment are
turning their attention to this problem in various ways,
not just through the industry,
but through academia, and not least through
the Dementia Research Institute that's just being set
up by the Medical Research Council in Alzheimer's,
the UK, in the United Kingdom.
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