Behaviour Diseases Environment Genetics Infectious diseases.
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Transcript of Behaviour Diseases Environment Genetics Infectious diseases.
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Behaviour
Diseases
Environment
Genetics
Infectious diseases
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Drug Discovery and BioMedical research in the 21st century?
The third revolution
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The first revolution:The era of incidental discoveries
1930s-1960s
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Aspirin
Felix Hoffman
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Penicillin
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The second revolution1970s-2000s
High throughput –
brute force screening of large libraries
of chemical compounds
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Future medicine- Targeted andPersonally “fitted” medicine –
Personalized Medicine
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Medicine of the 21st Century –
The 4P’s Medicine (Leroy Hood) Personalized,
Predictive, Preventive,
and Participatory Medicine
Stem cell-based therapies
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Breast Cancer – Estrogen Receptor Negative and Positive (predicts sensitivity to Tamoxifen)
Future medicine- Targeted andPersonally “fitted” and medicine - Personalized Medicine
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Herceptin (targeted)
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Fatal ADRs appear to be between the fourth and sixth leading cause of death in the USA
Prevalence rate of ADR
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Ageelderlychildrenneonates
Sex
High/Body Weight
ConcomitantDisease
Disease Process
Organ FunctionLiver, Kidney, Cardiac
Environmental Factors
diet / smoking / comedications
Inter-individual Variability in Drug
Response
Genetic polymorphisms
Factors determining inter-individual variations in drug response
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To understand it by pharmacogenomics
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Size of the entire Human Genome =3 Billion Bases
The Human Genome
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Central dogma of flow of genetic information DNA (the human genome)
RNA(the human transcriptome)
Proteins(the human proteome)
Multiple post-translational modifications:phosphorylations, acetylations, amidations, glycosylations, ubiquitinations, etc.
Epigenetic control of gene expression
Control by small RNAS
Is the development of personalized drugs going to be straightforward? Here are some major obstacles
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What are the obstacles – they appear to be broader and more complicated than just target identification
and validation :1. Many diseases (metabolic, psychiatric) are multi-
genic, and the causative connection between the genes products is not clear. We are still missing a whole body of basic knowledge.
2. Malignancies are characterized by genomic instability and therefore targets are not stable3. Human experimentation is complicated (HRT, stents)4. Lack of faithful animal models (neurodegeneration, cancer, metabolic diseases)5. Cost of developing new drugs - legal liability
(Vioxx/Celebrex), markets (new antibiotics), and patents protection (AIDS - South Africa, India)
6. End of blockbuster drugs era7. Bioethical problems of availability of genetic information