1. Epigenetic therapy in autoimmunity
An idea by Theodoros Savvidis

2. What is epigenetic therapy?
“Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. “
Many diseases including cancer, heart diseases, diabetes and mental illnesses are influenced by epigenetic mechanisms, and epigenetic therapy offers a potential way to influence those pathways directly.”

3. Epigenetic Therapies Agents
DNA-methyltransferases Inhibitors
HATs and HDACs Inhibitors
HMTs and HDMs Inhibitors
miRNA biomarkers and interventions
Inhibitors of other pathways (e.g. JAK-STAT)

4. Diseases known to have an epigenetic factor
Cancer
Type I Diabetes (Diabetic Retinopathy)
Cardiac Disfunction
Fear, Anxiety and Trauma
Schizophrenia
Etc…

5. Epigenetic drugs approved by FDA
Epi-drugs For example, high levels of sulphoraphane, an HDACi naturally found in broccoli sprouts has been associated with H3 and H4 hyperacetylation
Byrne et al. 2014

6. Two mechanisms of action of epi-drugs
Cherblanc et al. 2013

7. More Epigenetic Drugs in Trials
FDA approved!
Boumber & Issa 2011

8. Autoimmune Diseases More than 80 disorders described
Affecting ~7% of the population
Interplay between genetics and environment
Discordance of diseases between monozygotic tweens!

9. Epigenetics in Autoimmunity
Role of Th cells in autoimmunity
Role of the balance between the plastic lineages Th17 and Tregs
Reactivation of Tregs = good strategy against autoimmunity (HDAC9i against IBD, Mottet et al. 2003)
Treating Treg cells from psoriasis patients with HDAC inhibitor TSA showed prevented the Th17-like phenotype

10. Epigenetics in Autoimmunity
Type I Diabetes
Rheumatoid Arthritis
System Lupus Erythematosus
Multiple Sclerosis
Inflammatory Bowel Disease (e.g. Crohn’s Disease and Ulcerative Colitis)
Asthma
A microarray study by Miao et al. established the presence of an aberrant histone methylation profile in lymphocytes of T1D patients
Exposure to diesel exhaust particles (DEP) has been shown to change the overall DNA methylation profile in healthy elderly people

11. Epigenetics in Autoimmunity
Specific examples: HDACi’s in mouse models

12. Limitations Not all inhibitors are the same!
Specificity of the epi-drugs…
Not so effective in the forms of autoimmunity caused also by genetic factors
(huge variety of targets both histone and non-histone for e.g. HDMT and HDACs)

13. Why now?
Razvi and Oosta (2016)

14. Why now? National Institute of Health, Roadmap project in the US
European Union initiated Human Epigenome Project (HEP)
New Next Generation Sequencing technologies
HEP also focusing on environmental agents affecting gene expression…
Systematic, large scale epigenome projects such as the National Institute of Health Roadmap project in the US or the European Union initiated Human Epigenome Project (HEP) with the latter focusing on different cell types found in human blood will provide new insights into the epigenetic mechanisms.

15. Thank you!