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Behaviour Diseases Environment Genetics Infectious diseases

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Page 1: Behaviour Diseases Environment Genetics Infectious diseases
Page 2: Behaviour Diseases Environment Genetics Infectious diseases
Page 4: Behaviour Diseases Environment Genetics Infectious diseases

Behaviour

Diseases

Environment

Genetics

Infectious diseases

Page 5: Behaviour Diseases Environment Genetics Infectious diseases

Drug Discovery and BioMedical research in the 21st century?

The third revolution

Page 6: Behaviour Diseases Environment Genetics Infectious diseases

The first revolution:The era of incidental discoveries

1930s-1960s

Page 7: Behaviour Diseases Environment Genetics Infectious diseases

Aspirin

Felix Hoffman

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The second revolution1970s-2000s

High throughput –

brute force screening of large libraries

of chemical compounds

Page 11: Behaviour Diseases Environment Genetics Infectious diseases

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

Page 15: Behaviour Diseases Environment Genetics Infectious diseases

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)

Page 17: Behaviour Diseases Environment Genetics Infectious diseases

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

Page 19: Behaviour Diseases Environment Genetics Infectious diseases

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