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Printable Handouts
Navigable Slide Index
- Introduction
- Gene therapy for chronic pain
- The pain pathway
- Why HSV gene therapy for pain
- HSV is ideal for gene delivery to PNS
- Criteria for vector engineering and gene delivery
- Cascade regulation of HSV gene expression
- Latest generation of HSV vectors
- Non-toxic vector with persistent expression
- Gene therapy approaches to treat chronic pain
- Pain vector constructs
- Treating pain with opioid peptides
- Treating chronic pain at its source
- Spinal nerve ligation model of neuropathic pain
- Neuropathic pain testing
- L5 spinal nerve ligation
- Transduction of lumbar DRG with HSV vector
- SHPE provides antinociceptive effect
- Osteolytic sarcoma studies
- SHPE produces analgesia in sarcoma model
- Vector treatment & bone loss
- Phase I clinical trial in terminal cancer patients
- Phase I trial: outcome measures
- Gene therapy reduces pain in cancer patients
- Limitations of our pain gene therapy approach
- Glycine receptor silences neuronal activity
- Effect of glycine on nociceptive behavior
- Intravenous administration of glycine
- Glycine receptor alpha
- Ivermectin activation of GlyR-MUT vector
- GlyR summary
- Selective vector infection and expression
- Targeting transgene expression with promoters
- Vector design
- Gene expression constructs
- Promoter-regulated expression in embryonic DRG
- Promoter specificity in embryonic DRG
- Comparing LAP, CMV & CGRP gene expression
- CGRP-targeting: mCherry and CGRP
- Specificity for TRPV1+ neurons
- Talk summary
- Acknowledgements
Topics Covered
- HSV gene therapy for pain
- Criteria for vector engineering and gene delivery
- HSV gene expression and HSV vectors
- Treating pain with opioid peptides
- Spinal nerve ligation model of neuropathic pain
- Transduction of lumbar DRG with HSV vector
- Osteolytic sarcoma studies
- Clinical trial in terminal cancer patients
- Effect of glycine on nociceptive behavior
- Selective vector infection and expression
- Targeting transgene expression with promoters
- Gene expression constructs
- Promoter-regulated expression in embryonic DRG
- Comparing LAP, CMV & CGRP gene expression
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Glorioso, J.C. (2014, August 5). HSV vectors: approaches to the treatment of chronic pain [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 23, 2024, from https://doi.org/10.69645/LJIW3909.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Joseph C. Glorioso, Consultant: NuvoVec sri, Swich Bio, LLC Stock shareholder (self-managed): NuvoVec sri, Swich Bio, LLC
A selection of talks on Neurology
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Joe Glorioso.
I'm a professor at the
University of Pittsburgh School
of Medicine in
Pittsburgh, Pennsylvania.
And I've been working for the
last approximately 30 years
to develop gene delivery systems
based on herpes simplex virus.
And I'll be talking about the
application of a new generation
of viral vectors for the
treatment of chronic pain.
0:25
So what is pain, exactly?
Everybody knows it's an unpleasant
sensory and emotional experience,
which is adaptive, meaning
that it protects you
from further damage
or potential damage.
And the way pain is detected
is through a process
called nociception.
Nociception is the
sensory component of pain,
and it involves the peripheral
sensory nerves that detect pain
signals to deliver these
messages to the brain.
So pain perception is
a cognitive function.
It's the combination of
nociception and brain activity.
Chronic pain, on the other
hand, is not adaptive.
It's a pathological state
of peripheral nerves
that can be caused by injury or
inflammation, arthritis, cancer,
or nerve damage due to
neuropathy or injury.
And it has a broad penetrance
into the population.
There are more Americans
that experience chronic pain
at some times in their lives
than those with diabetes,
heart disease, and cancer combined.
1:28
So how does the pain pathway work?
Well, it turns out that there
are, in the dorsal root ganglia
which align the spinal cord, as
well as the trigeminal ganglia
in the face-- these have
special sensory fibers
called C fibers or A delta fibers.
And C fibers are
mostly non-myelinated,
whereas, A delta
fibers are myelinated.
And these are the nerve fibers that
receive pain signals, which can be
mechanical pressure, or extreme
temperatures-- hot and cold--
or caustic chemicals, or
inflammatory processes, and so on.
And these signals activate
receptors on the cells
that create an action potential.
And this delivers
neurotransmitters
to second order neurons
in the spinal cord.
And these pain signals are
delivered up through the spinal cord
into the cortex.
And it involves three orders
of neurons-- primary afferents,
second order neurons,
and third order neurons.
So the first pain
responses are rapid pain.
This is delivered by A delta fibers,
whereas, long-lasting chronic pain
responses are thought to
involve mostly C fibers.