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Summary of Preceding Alopecia Areata Research Summits

Summary of outcomes resulting from past summits and overview of the current state of alopecia areata research.

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Summary of Preceding Alopecia Areata Research Summits

  1. 1. Summary of preceding Alopecia Areata research summits Natasha Atanaskova Mesinkovska MD PhD Alopecia Areata Research Summit 2018
  2. 2. Alopecia areata - 3,500 years and Counting Kevin McElwee, PhD
  3. 3. Alopecia areata - 3,500 years and Counting • Causes: • Allergy • Immunity • Infectious • nerves and stress Kevin McElwee, PhD
  4. 4. ALOPECIA AREATA RESEARCH SUMMIT Forging the Future FINAL PROGRAM December 4-5, 2018 Alfred Lerner Hall, Columbia University
  5. 5. “Forging the future” • 2018 • Since 2008 - DECADE • 7th meeting
  6. 6. The history of Alopecia areata summit The idea: • Getting together interested scientist, clinicians and patients 1. Find treatment - cost effective 2. Advance research 3. Engage patients in therapeutic development
  7. 7. History of Alopecia areata summit: 2008
  8. 8. • The NAAF Registry!!! • Patient database • Repository of serum and DNA • NIH-funded whole genome scan
  9. 9. Foster collaboration
  10. 10. 2010
  11. 11. NAAF BOARD of DIRECTORS
  12. 12. The timeline of AA symposium • 2008 in Bethesda- Genetics and Immunology • 2009 in Denver - Immunology, animal models, drugs used in other diseases. • 2010 in NYC- demand of new treatments by AA patients. • What tools were needed to foster clinical research – tools, biomarkers, outcome measures.
  13. 13. The timeline • 2012 in Bethesda – • consolidating the recently uncovered mechanisms in AA • targeted by modern therapies used in other diseases • Development of core uniform protocol.
  14. 14. The timeline • 2014 in Bethesda • Larger meeting, 90 participants • New drugs showing promising results in AA • New technologies and directions • Clinical trials • 2016 in NYC • Advanced genetics and immunology • New animal models • Epidemiology • QOL • translational research • First Summit: Industry partners!
  15. 15. Nine industry representatives! Session 5 – Industry Roundtable 152016 AA Research Summit Nine industry representatives! Stakeholder support of new products for alopecia areata. Engaging the patient voice in therapeutic development. Company Speaker Title Aclaris Therapeutics, Inc. Dr. Kimberley Forbes-McKean Senior Vice President, Drug Development BiologicsMD, Inc. Mr. J. David Owens President & CEO Concert Pharmaceuticals, Inc. Dr. Roger Tung Co-Founder, President & CEO Gilead Sciences, Inc. Dr. Thomas O'Riordan Senior Director, Clinical Research Incyte Corporation Dr. Richard L. Leff Group VP, Drug Development Legacy Healthcare Mr. Saad Harti President LEO Pharma Inc. Dr. Michael Sierra Vice President, LEO Science & Tech Hub Pfizer, Inc. Dr. Elena Peeva Executive Director, Inflammation & Immunology Clinical Research RXi Pharmaceuticals Corp Dr. Geert Cauwenbergh President & CEO
  16. 16. Basic Science Clinical Trials Patient Focused Regulatory
  17. 17. Basic Science Clinical Trials Patient Focused Pharmaceutical
  18. 18. Ralf Paus: Revising the Immune Privilege Hypothesis • New physiological role of gamma delta T cells • Scout for stressed hair follicle signals • Langerhans cells, Mast cells, among others. • a step toward a truly ‘curative’ therapy • would involve restoration of peripheral tolerance
  19. 19. Marta Bertolini
  20. 20. Michael Rendl: Niche Control of HF Formation and Regeneration • hair regeneration wave profiling • Hair-GEL.net • resource to catalogue hair genes • Searchable database for candidate AA genes/antigens • 14 different cell types in adult HF
  21. 21. Emma Guttman: Cytokine Targeted Therapy: Lessons from AD and Other Diseases • Atopic dermatitis (AD) • Highest comorbidity for AA (38%). • IL13 SNPS and Th2 cytokines • Dupilumab – Atopic dermatitis and AA. • Apremilast ? • Ustekinumab: ? higher dose in AD than psoriasis.
  22. 22. John Harris: Understanding Parallels between Vitiligo and AA
  23. 23. Amos Gilhar: Non-conventional T-cells in the Pathogenesis of AA • NKG2D expressed also on ILCs • humanized mouse AA model • iNKT cells in AA • New inexpensive treatments: Alpha-GalCer
  24. 24. Amos Gilhar: Non-conventional T-cells in the Pathogenesis of AA • NKG2D expressed also on ILCs • humanized mouse AA model • iNKT cells in AA • New inexpensive treatments: Alpha-GalCer
  25. 25. So much more… • Annemieke de Jong: Identifying Pathogenic TCRs in AA • Natasha Botchkareva: Role of miRNAs in AA • Dan Kaplan: T cells, DCs Autoimmunity and the Hair Follicle • Alessandro Sette: Epitope Identification Screening in AA • Anastasia Khvorova: RNA Chemistry toward Modulation of Gene Expression in Skin • Tiffany Scharschmidt: Commensal Microbes and HF Morphogenesis Drive Treg Migration into Skin • Michael Rosenblum: Tregs in Skin and HF Stem Cell Differentiation
  26. 26. Basic Science Clinical Trials Patient Focused Pharmaceutical
  27. 27. Madeleine Duvic: Update on AA Registry • 11,180 AA patients • All subtypes of AA: AU 40%; AT 20%; AAP 40% • All ethnic/racial groups represented. • DNA, serum samples • 6000 patients -not yet sampled • re-contacted for participation clinical trials. • Lynn Petukhova: Comorbidities in the AA Registry
  28. 28. George Cotsarelis: Nutritional Factors Influencing Alopecia • Optimum conditions for hair shaft formation • Micronutrients • Vitamin D, Zinc, Iron. • Is telogen effluvium a trigger for AA?
  29. 29. Angela Christiano: Update on Genetics and Immunology • GWAS studies • At least 14 genes involved in AA • Environmental factors: microbiome
  30. 30. Christiano 2016
  31. 31. “YAK YAK YAK about JAK JAK JAK” • Cleveland, Columbia, Duke, Stanford, Yale • Response rates: consistent across sites (range 50-75%): • Heterogeneous groups of patients: • duration of disease • dosing regimens • length of treatment
  32. 32. JAK inhibitors clinical trials • Cleveland: tofacitinib 54% • Columbia: tofacitinib 65%, ruxolitinib 75% • Duke/Incyte: topical JAK ~50% • Stanford: tofacitinib 66% • Yale: tofacitinib 60% adults, 75% adolescents
  33. 33. JAK Take Home Lessons: from Combined Studies • Relapse after treatment in all studies • sometimes worse than baseline, 4-8 weeks after stopping • Flares while on treatment • 12% in Yale • Ruxolitinib patients regrowth visible earlier than tofacitinib • Tofacitinib required dose escalation, longer treatment periods. • Responses with long duration of disease • ? suggested that <10 years better responses • Regional differences in regrowth: Eyebrows, lashes and body and facial hair • Combo : pulse prednisone Q4 weeks for 3 doses (Yale) , ILK ( NYU). • No reported improvement in AGA . • AE: generally mild. • Acne (8% Yale ),trace hematuria (Columbia), eczema herpeticum (Stanford); LFT, lipid abnormality (Cleveland), URIs.
  34. 34. Terrific talks • Jerry Shapiro: Microneedling and PRP • Ali Jabbari: Biomarkers for AA and Clinical Trials • Antonella Tosti: Repurposing Drugs for AA – Vytorin • Teresa DiLorenzo: Similarities Between Diabetis Type 1 and AA • Leslie Castelo-Soccio: Using Computer Vision to Quantitate Pediatric AA • Tito Mendoza: Update on the Use of the AA Symptom Impact Scale • Elise Olsen: A new visual Aid for Assessing Hair Loss in AA
  35. 35. Basic Science Clinical Trials Patient Focused Pharmaceutical
  36. 36. Angela Rodgers: What Treatment Means to Patients • No safe, affordable, accessible treatment is a problem • “a magnificent effect on psychological status” • socialization from childhood to adulthood • (Shahin, A. et al., 2014). • Increased prevalence of mental health issues
  37. 37. Basic Science Clinical Trials Patient Focused Regulatory
  38. 38. Regulatory • NIH • NIAMS • FDA • PCORI • Industry • Medical economic • Health Insurance
  39. 39. Thank You natasha@naaf.org

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Summary of outcomes resulting from past summits and overview of the current state of alopecia areata research.

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