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Printable Handouts
Navigable Slide Index
- Introduction
- What is a parasite?
- Parasitos
- Modern definition of parasites
- What is a “neglected disease”?
- Neglected tropical diseases
- Challenges of antiparasitic drug development
- Time and cost of drug development (1)
- Neglected tropical diseases example
- Mendoza province, Argentina 1840
- Chagas’ disease
- Chagas’ disease (T. cruzi)
- Chagas' disease (life cycle)
- Discovering drugs for Chagas' disease
- Approach #1 target based drug design
- Target-based approach
- Target protease biology
- Parasite stages
- Screening for novel inhibitors by molecular docking
- Virtual ligand libraries
- Docking poses
- Industry collaborations for NTD drug discovery
- Protease inhibitor
- Ascites after heart failure in T.cruzi infected mice
- Untreated mouse heart cells
- Treated mouse cells
- Dogs infected with T. cruzi
- Cruzain
- Western blot of protease in parasite cells
- Golgi apparatus swelling
- Time and cost of drug development (2)
- Rapid translation
- From lead to clinical candidate
- Who is backing the effort?
- Approach #2
- Luciferase assay for T. brucei
- Identify parasite within host cells
- Similar assays for all kinds of organisms
- FDA drug library screen vs. T. brucei
- Repurposing FDA approved drugs
- Iconix library screening against E. histolytica
- Iconix library hits against E. histolytica
- Image capture analysis
- Natural product lead discovery- U.C. Santa Cruz
- QB3 – accelerating translational innovation
- Acknowledgments
- Support & Collaborators
Topics Covered
- The challenges of discovering and developing drugs for neglected tropical diseases
- What is meant by a “neglected tropical disease”?
- Identification of the organisms responsible for neglected tropical diseases
- Alternative approaches to drug discovery including both target-based approach and phenotypic approach
- Specific examples for drug leads or drug candidates discovered by these approaches
- Repurposing of existing drugs for use against neglected tropical diseases.
Links
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Therapeutic Areas:
Talk Citation
Mckerrow, J. (2014, October 7). The challenge of developing drugs for neglected parasitic diseases [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 22, 2024, from https://doi.org/10.69645/HIGU6811.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. James Mckerrow has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Pharmaceutical Sciences
Transcript
Please wait while the transcript is being prepared...
0:00
This is James H. McKerrow from the
UCSF Center for Drug Discovery.
I'm giving a talk on the
challenge of developing
drugs for neglected
parasitic diseases.
0:14
We're going to be talking
about parasitic diseases today,
so what is a parasite?
0:20
Parasite comes from the
Greek word, parasitos.
which is the name of a class
of priests who had meals
at public expense-- this, according
to Clitodemus, an ancient writer.
And certainly, by this
definition, probably all of you
have met a parasite in your life.
0:39
But the modern
definition of parasite
refers to eukaryotic
organisms that can range
from very simple single-cell
protozoa, such as malaria
and the trypanosomes, to very
complex multicellular worms,
including roundwarms,
the nematodes, flatworms,
the platyhelminths, and
cestodes, the tapeworms.
1:02
So we've defined parasite.
Let's define what we mean
by a neglected disease.
1:08
Neglected tropical diseases
are diseases in which there are
no effective drugs, no safe
drugs, or there's drug resistance.
This is despite the fact that these
are diseases that affect hundreds
of millions of people
worldwide, making
them major global health problems.
In addition, for many
of these diseases,
there is currently no
adequate diagnostic test.
And for virtually all of them,
there is no effective vaccine.
So why is it that if diseases,
such as shown in this slide,
affect so many million people,
we don't have effective drugs?