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Printable Handouts
Navigable Slide Index
- Introduction
- Review of work
- Purines as PD protectants
- Purines & Parkinson’s
- Where we are today
- Pursuing Epi clues to protection for Parkinson’s
- Caffeine (1)
- Coffee, tea and the risk of PD
- Parkinson disease in twins
- Coffee and caffeine intake and the risk of PD
- Caffeine consumption and risk of PD
- PD & caffeine habit
- Possible explanations for inverse association
- MGH molecular neurobiology lab (1999)
- Effect of caffeine in MPTP mouse model of PD
- Caffeine and gender effect in PD
- Exposure of caffeine in postmenopausal women
- MGH molecular neurobiology lab (2003)
- Estrogen replacement and caffeine in MPTP model
- Caffeine targets in humans
- CSC reverses MPTP neurotoxicity
- Adenosine A2A receptor KO in the MPTP model
- MGH molecular neurobiology lab (2006)
- TH+ neuron loss and adenosine A2A receptor
- Potential benefits of A2AR blockade in PD (1)
- Caffeine and A2A receptors in models of PD
- Potential benefits of A2AR blockade in PD (2)
- Brain distribution of adenosine receptors
- Brain distribution of non-DA receptors targeted
- A2A antagonists in clinical trials for PD
- Potential benefits of A2AR blockade in PD (3)
- Caffeine consumption & the risk of dyskinesia
- Potential benefits of A2AR blockade in PD (4)
- Urate
- HSPH Neuroepi group
- Urate oxidase mutations during primate evolution
- Advantage of higher urate?
- Epidemiology of urate and PD (1)
- Epidemiology of urate and PD (2)
- Meta-analysis of cohort studies
- The observation and the hypothesis
- Serum urate predicts progression of PD
- higher urate predicts a slower PD progression
- Results of the study
- Functional imaging in PD
- SPECT images
- Higher urate at baseline and DA binding sites
- Urate in PRECEPT study
- Parkinson study group (PSG) ~1986
- CSF and serum urate as predictors of progression
- Hazard ratios of reaching primary endpoint
- Urate and other neurodegenerative diseases
- Urate in PD: summary and translational potential
- Urate prevents dopaminergic neuron death
- Our investigating group - Sara Kipriani
- Astrocytes potentiate neuroprotective effects
- Urate prevents dopaminergic neuron degeneration
- Our investigating group - Shi Chuan Chen
- Brain urate in UOx knockout mice
- UOx KO reduces neurotoxicity in 6-OHDA model
- Transgenic UOx exacerbates toxicity
- Urate in PD: summary and translational potential
- Safety of URate Elevation in PD: SURE-PD
- The Gout by James Gillray (1799)
- Serum urate is a predictor of progression in PD
- CONSORT diagram for the SURE-PD
- Safety – serious adverse events (SAEs)
- Target engagement (1)
- Target engagement (2)
- SURE-PD: secondary results, clinical scales
- SURE-PD - conclusion
- UPping URate Safely in PD: UpUrS-PD
- Purines as PD protectants - summary
- MNL Parkinson’s research group at MGH MIND
Topics Covered
- Purines in Parkinson's: from epidemiology of caffeine and urate to therapeutics
- Purines as PD protectants
- Purines & Parkinson’s
- Pursuing Epi clues to protection for Parkinson’s
- Coffee, tea and the risk of PD
- Caffeine consumption and a reduced risk of PD: Possible explanations for this inverse association – Caffeine, post-menopausal estrogen and risk of Parkinson’s disease
- Caffeine targets in humans
- CSC reverses MPTP neurotoxicity
- Adenosine A2A receptor KO mimics caffeine’s protective effect in the MPTP model of PD
- Potential benefits of A2AR blockade in PD
- Caffeine and A2A receptors in models of PD
- Brain distribution of adenosine receptors
- Brain distribution of adenosine receptors
- Industry A2A antagonists advancing to clinical trials for PD
- Caffeine consumption & the risk of dyskinesia in PD
- Urate oxidase mutations during primate evolution
- Advantage of higher urate?
- Epidemiology of urate and PD
- Serum urate predicts progression of Parkinson’s disease
- higher urate predicts a slower rate of PD progression
- Functional imaging can identify dopaminergic deficits of PD
- Higher serum urate at baseline predicts a slower rate of losing DA transporter binding sites in PD
- CSF and serum urate as predictors of progression of Parkinson’s disease
- Is urate a predictor of slower progression in other neurodegenerative diseases?
- Urate prevents dopaminergic neuron death in primary cultures of midbrain neurons
- Astrocytes potentiate the neuroprotective effects of inosine and urate
- Urate prevents MPP+-induced dopaminergic neuron degeneration
- SURE-PD study
- UpUrS-PD study
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Schwarzschild, M. (2014, June 2). Purines in Parkinson's: from epidemiology of caffeine and urate to therapeutics [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 6, 2024, from https://doi.org/10.69645/LGFH3557.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Michael Schwarzschild has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Neurology
Transcript
Please wait while the transcript is being prepared...
0:00
Hello.
My name is Michael Schwarzschild,
at Massachusetts General Hospital,
in Boston.
And I am pleased to present
our work, and that of others,
on purines in Parkinson's disease,
from epidemiology of caffeine
and urate to therapeutics.
As by way of disclosure, I have
no financial conflict of interest
or commercial relationship,
relevant to this presentation.
0:28
I will review for you some of
the work from our laboratory
on the Charlestown Navy Yard
campus of MassGeneral Hospital
and the MassGeneral Institute
for Neurodegenerative Disease.
But most of the work that
I'll be talking about
reflects attributions
across disciplines
and with many collaborators.
As you can see here, in addition
to the signature USS Constitution
from the Navy Yard, there is also
at an early stage, the Lenny Zakim
Bridge, that connects the
Charlestown Navy Yard to Boston
and MassGeneral Hospital proper,
that we've adopted over the years,
as a metaphor for the
translational work that we do.
1:11
Here you can see
some of the art work
that was kindly donated by
a local artist, Don Eyles,
depicting that metaphor during its
construction over a decade ago now,
and again reflecting our
translational goals in year focused
on purines as protectants
in Parkinson's disease.
And so, over the course
of the talk, broadly I'll
hope to illustrate how epidemiology
of reduced risks of Parkinson's
disease, in particular, are
valuable clues for developing novel
therapies to slow
progression of the disease.
And then I'll give an overview of
two examples that we've pursued,
one adenosine A2A
receptor antagonism,
with caffeine being a nonspecific
adenosine A2A antagonist,
having emerged as a realistic
multi-faceted potential new therapy
on the threshold of clinical
use in Parkinson's disease.
In the second half, I'll focus on
another example of how urate has
emerged really originally
from its biology in evolution,
to clues that have been
pursued in the laboratory,
and by epidemiologists, with the
convergence of those findings,
leading us to pursue
clinical application.
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