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Centre of Preventive Doping Research Next Generation Gene Doping Myths and Facts Patrick Diel Center of Preventive Doping Research Dept. Molecular and Cellular Sports Medicine German Sports University Cologne
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Page 1: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Next Generation Gene Doping

Myths and Facts

Patrick Diel

Center of Preventive Doping Research

Dept. Molecular and Cellular Sports Medicine

German Sports University Cologne

Page 2: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Next Generation Gene Doping

Myths and Facts

Patrick Diel

Center of Preventive Doping Research

Dept. Molecular and Cellular Sports Medicine

German Sports University Cologne

Page 3: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Physical performance

Sceletal muscle

OxygenEnergy

Anabole Steroids EPO PPARs

Cognitive Abilitys

Methylphenidat

Zürich 2017

Page 4: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Zürich 2017

Page 5: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Doping is defined as the

occurrence of one or more of the

anti-doping rule violations set forth

in Article 2.1 through

Article 2.8 of the Code.

Zürich 2017

Page 6: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

?Zürich 2017

Page 7: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Zürich 2017

Page 8: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Genes and Sport

Eero Mäntyranta: Mutation in the Epogene results in extraordinary physical

performance

Analysis of the

induividual genetic

predisposition to

increase physical

performance

Gene Analysis

Manipulation of the

gene activity to

increase physical

performance

Gendoping

Zürich 2017

Page 9: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Zürich 2017

Page 10: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Gene doping = Gene therapy ?

Zürich 2017

Page 11: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Gene doping vs. Gene therapyGene doping vs. Gene therapy

Gene therapy:

• Aim, Treatment of Diseases

• Risk and Befit must be in a balance

Gene doping:

• Aim, Increase of physical performance.

• Normally healthy powerful people are treated

• It is easier to increase performance than tu cure a life-threatening disease

• Doping is illegal, ethical aspects are not relevant

Zürich 2017

Page 12: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

What is the difference between gene doping and doping ?

The issue of definition taking hematocrit as an example

Old fashion: Blood transfusion

Old fashion : recombinant EPO

The future: Modulation of endogenous Gene activity (HIF stabilizer's).

The future : Gene therapy?

Reality: Drug development based on gene therapy

is stopped. To risky to expensive , not efficient.

Zürich 2017

Page 13: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Moreover according to the

Wada definition the following

techniques also can be

defined to be gene doping

• Every kind of stem cell therapy

• siRNA techniques

• Techniques involving epigenetic modifications

• CRISPR / Cas9 techniques

Zürich 2017

Page 14: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Doping NewsSalbutamol

Trimetazidine

Meldonium

Zürich 2017

Page 15: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

New drugs and therapies : the real challenge

Zürich 2017

Page 16: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Zürich 2017

Page 17: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Myostatin

Zürich 2017

Page 18: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Sceletal muscle dystrophy

Metabolic Syndrome

Sarkopenia

Injurie treatment

Animal breeding

Zürich 2017

Page 19: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Multiple Ascending Dose Phase 1 Study - A study in healthy postmenopausal women (A031-02), evaluating multiple doses of ACE-031

Zürich 2017

Page 20: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Myostatin Inhibition

Chemical modification of DNAGen KO Termination of

transkription

siRNA

Blocking

Antibody

(Wyeth)

Overexpression of

Follistatin

Rezeptor

antagonists

Manipulation of the

processing

Application of

rekombinat propeptide

/AG Research)

Soluble ACTII B

(Acelleron)

Zürich 2017

Page 21: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Identifying doping abuse

Direct detection of

abused drug or

metabolites

Indirect detection by

biomarker analytics

Zürich 2017

Page 22: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Zürich 2017

Page 23: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Zürich 2017

Page 24: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Zürich 2017

Page 25: Next generation gene Doping - molekularediagnostik.ch · Myostatin Inhibition Chemical modification of DNA Gen KO Termination of transkription siRNA Blocking Antibody (Wyeth) Overexpression

Centre of Preventive Doping Research

Conclusions:

•The identification of new doping relevant molecular targets, the increase in molecular and cellular techniques and finally the introduction of new therapies and drugs, let to an exponential

increase in the complexity of doping.

•This is the real great challenge in the future fight against doping.

•Gene doping as defined by WADA is only a very limited part of the problem

• Combination of established detection sytems with biomarker monitoring and new detection techniques is a promising strategy in the future fight against doping

Erlangen 22.07.2016


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