Individualisierte Medizin am Inselspital Genetik und Perioperative Medizin

Sind wir alle gleich ?

Oder Individuen ?

1.000.000 B.C - 2003

Auch wenn es verwirrt und oft keinen Sinn macht....

.... sind wir so individuell , wie unsere DNA !

3,2 mrd. Basenpaare etwa 25.000 Gene Das humane Genom 3,2 mrd. Basenpaare etwa 25.000 Gene

... aber es wurde lange ignoriert !

.... das komplexe Erkrankungen Die meisten komplexen Erkrankungen haben einen komplexen genetischen Hintergrund. Multiple genetische Faktoren tragen gemeinsam mit Umwelteinflüssen zu Inzidenz und Verlauf bei. Canabis abuse has been shown to go along with an increased risk for schizophrenia, and it seems that canabis abuse is not an early sign for schizophrenia, but that it actually increases the risk for schizophrenia. A low IQ has also been repeatedly reported to be a risk factor for schizophrenia. But as you can see here; the largest risk factor known today is still to be a first degree relative of a patient with schizophrenia. Children and siblings have a relative risk of 5-10 and a monozygote twin even 42-60.

....genetische Ursachen haben!

.....quod erat demonstrandum !

...und die Ergebnisse auch !

Medikamente werden verordnet als wären alle gleich Based on: Signs and symptoms Average response Consequence: Some respond others do not some have adverse events

Response rates of major drugs for important diseases often <50%! Spear et al., 2001 BMJ

Verordnen falscher Medikamente birgt auch Risiken Account for 5% of all hospital admissions Occur in 10 - 20% of hospital inpatients (USA: 2 mio cases in 1994) Cause of death in 0.1 % of medical inpatients (USA: 100‘000 deaths 1994) Among top ten causes of death in hospital inpatients Pirmohamed et al., 1998 BMJ

Nature. 2004 May 27;429(6990):464-8. Moving towards individualized medicine with pharmacogenomics. Individuals (DNA`s) respond differently to drugs and sometimes the effects are unpredictable. This intersection of genomics and medicine has the potential to yield a new set of molecular diagnostic tools that can be used to individualize and optimize drug therapy.

Pharmacogenetics /-genomics Variation in drug response Genetic factors Environmental & Biological factors Drug interactions Metabolism Transport Drug target Cell Drugs Linking the information on the variation of human genes to variation in clinical responses to drugs

Translational medicine „Is the continuum – often known as “bench to bedside” – by which the biomedical community takes a focused point of view to move research discoveries from the laboratory into clinical practice to diagnose and treat patients.“

Was ist das neue an dem Konzept? Altes Paradigma: Ein Medikament hilft vielen viel. Neues Paradigma: Wir identifizieren das richtige Medikament für den richtigen Patienten.

Identification of the right drug and dose `Individualized Medicine‘

Was gehört zur Translationalen Medizin: A scientific search to discover the origins and mechanisms of disease The identification of and insight into specific biological events, biomarkers, or pathways of disease Systematically discover and develop new diagnostics and therapeutic methods and products. The adoption of such new diagnostic and therapeutic approaches into the routine standard of care.

Microchip

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Hybridisierung der DNA

Example of good clustering

Maligne Hyperthermie (MH) Lebensbedrohliche hypermetabole Stoffwechselstörung Azidose Hyperkapnie Hypoxämie Rigor Rhabdomyolyse Elektrolytentgleisung Herz-Kreislauf-Störungen Fieber

Maligne Hyperthermie (MH) Auslöser: volatile Anästhetika Succinylcholin Defekt der myoplasmatischen Ca-Homöostase autosomal dominanter Erbgang Punktmutationen im Ryanodinrezeptor z.B. ein Basenaustausch C 1840 T im RYR1 Gen Inzidenz 1 : 15.000 bis 1: 60.000

Genetik und Pathophysiologie der Sepsis Assoziation mit TNF Plasmaspiegeln Menges et al., CCM, May 2008

ELPIS Projekt = weniger Schmerz + Nausea nach OP

Lung Tumor retention after injection of (radiolabeled MADB106+3 weeks) In rats, halothan + morphin vrs spinal anesthesia + morphin, breast adeno adenocarcima cells injected which metastazise only to lungs, tx cell retention after 24hours and 3 weeks Bar-Yosef S. Anesthesiology. 2001 Jun;94(6):1066-73.