Summary, outcomes and action plan presented by Dr. Angela Christiano at the end of the two-day Alopecia Areata Research Summit held November 14-15, 2016 in New York, NY.
Dr. Maria Hordinsky provides an informative, straightforward presentation of everything you need to know about alopecia areata, including risks and benefits of current and evolving off-label treatment options. Dr. Hordinsky is Professor and Chair of the Department of Dermatology at the University of Minnesota and is recognized for her clinical expertise in alopecia areata.
Drug-induced hypersensitivity syndrome (DIHS)/Drug reaction with eosinophilia and systemic symptoms (DRESS)
Presented by Pongsawat Rodsaward, MD.
December 17, 2021
Overview of options available to treat pediatric and adult alopecia areata, including the risks and benefits of current and evolving off-label treatment options with the understanding that there is currently no treatment approved by the FDA for this disease.
Dr. Maria Hordinsky provides an informative, straightforward presentation of everything you need to know about alopecia areata, including risks and benefits of current and evolving off-label treatment options. Dr. Hordinsky is Professor and Chair of the Department of Dermatology at the University of Minnesota and is recognized for her clinical expertise in alopecia areata.
Drug-induced hypersensitivity syndrome (DIHS)/Drug reaction with eosinophilia and systemic symptoms (DRESS)
Presented by Pongsawat Rodsaward, MD.
December 17, 2021
Overview of options available to treat pediatric and adult alopecia areata, including the risks and benefits of current and evolving off-label treatment options with the understanding that there is currently no treatment approved by the FDA for this disease.
Different pathways might drive the inflammation in alopecia areata and clinical trials utilizing narrow-targeted
therapeutics will be able to elucidate the role of each cytokine pathway in the disease phenotype.
Genetic and epigenetic biomarkers for therapeutic monitoring in neurological ...Pranav Sopory
Seminar held on Genetic and epigenetic biomarkers for therapeutic monitoring in neurological disorders.
Multiple Sclerosis, Alzheimer's Disease and Parkinson's Disease.
Biomarkers and epigenetic explained. New epigenetic drug targets.
Disorders of the hair shaft present with a challenge while understanding the topic and also while diagnosing any patient presenting with a similar problem. This presentation makes the approach to any patient presenting with hair shaft disorders more comprehensive.
Presentación sobre el láser médico de diodo para depilación "Vectus", a cargo de la Dra. Josefina Royo de la Torre, subdirectora de Instituto Médico Láser, en el VI Simposio de Palomar Medical Inc.-
Presentation "Vectus Diode Laser": details of the new system for permanent hair removal.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
To date, the Registry has epidemiology and quality-of-life data from 11,180 self-registered patients with 4,196
well-characterized samples of DNA, lymphoblast lines, and sera for future research studies.
Different pathways might drive the inflammation in alopecia areata and clinical trials utilizing narrow-targeted
therapeutics will be able to elucidate the role of each cytokine pathway in the disease phenotype.
Genetic and epigenetic biomarkers for therapeutic monitoring in neurological ...Pranav Sopory
Seminar held on Genetic and epigenetic biomarkers for therapeutic monitoring in neurological disorders.
Multiple Sclerosis, Alzheimer's Disease and Parkinson's Disease.
Biomarkers and epigenetic explained. New epigenetic drug targets.
Disorders of the hair shaft present with a challenge while understanding the topic and also while diagnosing any patient presenting with a similar problem. This presentation makes the approach to any patient presenting with hair shaft disorders more comprehensive.
Presentación sobre el láser médico de diodo para depilación "Vectus", a cargo de la Dra. Josefina Royo de la Torre, subdirectora de Instituto Médico Láser, en el VI Simposio de Palomar Medical Inc.-
Presentation "Vectus Diode Laser": details of the new system for permanent hair removal.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
To date, the Registry has epidemiology and quality-of-life data from 11,180 self-registered patients with 4,196
well-characterized samples of DNA, lymphoblast lines, and sera for future research studies.
Study: The Future of VR, AR and Self-Driving CarsLinkedIn
We asked LinkedIn members worldwide about their levels of interest in the latest wave of technology: whether they’re using wearables, and whether they intend to buy self-driving cars and VR headsets as they become available. We asked them too about their attitudes to technology and to the growing role of Artificial Intelligence (AI) in the devices that they use. The answers were fascinating – and in many cases, surprising.
This SlideShare explores the full results of this study, including detailed market-by-market breakdowns of intention levels for each technology – and how attitudes change with age, location and seniority level. If you’re marketing a tech brand – or planning to use VR and wearables to reach a professional audience – then these are insights you won’t want to miss.
UX, ethnography and possibilities: for Libraries, Museums and ArchivesNed Potter
These slides are adapted from a talk I gave at the Welsh Government's Marketing Awards for the LAM sector, in 2017.
It offers a primer on UX - User Experience - and how ethnography and design might be used in the library, archive and museum worlds to better understand our users. All good marketing starts with audience insight.
The presentation covers the following:
1) An introduction to UX
2) Ethnography, with definitions and examples of 7 ethnographic techniques
3) User-centred design and Design Thinking
4) Examples of UX-led changes made at institutions in the UK and Scandinavia
5) Next Steps - if you'd like to try out UX at your own organisation
Published Research, Flawed, Misleading, Nefarious - Use of Reporting Guidelin...John Hoey
Much published health sciences literature is misleading and biased
Efforts to correct this include use of reporting guidelines- criteria for doing science and reporting the results properly
Also discussion of conflicts of interest - how to report them.
Visualization Tools for the Refinery Platform - Supporting reproducible resea...Nils Gehlenborg
The Refinery Platform (http://www.refinery-platform.org) is a web-based data visualization and analysis system for epigenomic and genomic data designed to support reproducible biomedical research. The analysis backend employs the Galaxy Workbench and connects to a data repository based on the ISA-Tab data description format. In my talk I will discuss the exploratory visualization tools that we have integrated into Refinery.
PRA Insights Report: Alzheimer's Disease ResearchEmma Whieldon
This PRA Insights report focusing on Alzheimer’s disease research was compiled from survey data gathered at the 2017 Alzheimer’s Association International Conference (AAIC). The aim of the survey was to gather insight on clinical development and the future of research in Alzheimer’s disease from pharma and biotech, academic researchers, next generation investigators, clinicians and the care research community involved in the prevention and treatment of Alzheimer’s disease and other dementias.
PDCD is an abbreviation for pyruvate dehydrogenase complex deficiency, a genetic mitochondrial disorder in children which is frequently associated with lactic acidosis and neurological/neuromuscular symptoms.
Session Two: Barriers to investment in research to find a disease modifying therapy or cure for dementia
Dr Neil Buckholtz , Director of Neuroscience, the National Institute on Aging (NIA), National Institutes of Health (NIH)
Leveraging Publicly Accessible Clinical Trails Data Sharing, Dissemination an...Vaticle
In the broader realm of the advancement of science and the betterment of the human condition, there are several purported benefits for sharing clinical trials and research data. The scientific community has just begun to embrace open-access datasets to build their knowledge base, gain insight into new discoveries, and generate novel data-driven hypotheses that were not initially formulated in the studies. With the increasing amount of clinical trial data available, comes the need to leverage a multitude of shared datasets. Your knowledge base needs to facilitate discovery across research domains.
This talk highlights the data sharing, dissemination, and repurposing of clinical and molecular studies generated by government-funded research consortia. Further, we are building a new knowledge base resource, IMMGRAKN to facilitate translational discovery from crowd-sourced clinical trials data in ImmPort (www.immport.org), an NIH-NIAID funded open-access immunology database and analysis portal. The case studies demonstrating the use of IMMGRAKN will be discussed
Brady’s white paper provides valuable industry examples on how label failure impacts labs and offers effective solutions to mitigate sample loss and improve efficiency. The report explains industry regulations that are in place to improve lab practices and explores how the use of barcoding systems, label materials designed for lab environments and printed label information can reduce sample errors.
Similar to Alopecia Areata Research Summit Summary (20)
Dr. Angela Christiano presented an update on genetic and immunological studies in alopecia areata. Her research is focused on defining the genetic basis of alopecia areata to clarify how the disease develops—a key initial step toward creating novel therapies. Dr. Christiano is the Richard and Mildred Rhodebeck Professor of Dermatology, Genetics and Development, Vice Chair for Basic Science Research in Dermatology, and Director of the Center for Human Genetics at Columbia University.
Dr. Leslie Castelo-Soccio presented an overview of what parents need to know about alopecia areata in children and adolescents, including the differences between pediatric and adult patients, and the risks and benefits of current and evolving off-label treatment options. Dr. Castelo-Soccio is Assistant Professor of Pediatrics and Dermatology at the University of Pennsylvania School of Medicine and head of the Pediatric Hair Clinic and Director of Research in Pediatric Dermatology at the Children’s Hospital of Philadelphia. Her clinical and academic research focus is on pediatric hair disorders.
Dr. Maria Hordinsky presented an overview of key things adults need to know about alopecia areata, including the risks and benefits of current and evolving off-label treatment options. Dr. Hordinsky is Professor and Head of the Department of Dermatology at the University of Minnesota. She is recognized for her clinical expertise in alopecia areata and hair diseases.
Dr. Natasha Mesinkovska, NAAF’s Chief Scientific Officer, presented the latest progress of NAAF’s Treatment Development Program and how your involvement is critical to developing treatments for alopecia areata. In addition to overseeing NAAF’s research efforts, Dr. Mesinkovska is Director of Clinical Research in Dermatology at the University of California Irvine.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Presented at the joint International Eczema Council and National Alopecia Areata Foundation Symposium, "Atopic Dermatitis and Alopecia Areata: Comparison and Contrast”, held during the 2019 Annual American Academy of Dermatology meeting in Washington, DC to explore the similarities and differences between these two common but complex skin diseases and the implications from bench to bedside.
Discussion of the immune privilege collapse model of alopecia areata pathogenesis, available evidence to support this hypothetical scenario, and promising avenues for future investigation.
The FDA plans to prioritize improvements in the quality of demographic subgroup data collection, reporting and analysis, encourages greater participation of diverse patients, and supports the transparency of subgroup data. To this end, ways to recruit, engage, educate, and study those of diverse backgrounds to alopecia areata trials will be discussed.
Measuring willingness to pay in patients with alopecia areata to gauge their willingness to pay out of pocket for a cure or control of their condition.
While genome-wide association studies of common genetic variants in alopecia areata have highlighted etiological contributions from specific immune cells and pathways, exome studies of rare variants in patients and family members are implicating components of the hair follicle extracellular matrix, suggesting a crucial point of communication between the hair follicle and the immune system.
Novel induction of alopecia areata in C3H/HeJ mice shows a potential role of previously unrecognized endogenous SSEA-positive myeloid cells in driving inflammatory cascade and hair loss mechanisms.
Through in-depth interviews of key informant groups, Lilly developed a five-grade investigator global assessment (IGA) scale to measure clinically meaningful treatment response to alopecia areata treatment for patients with ≥ 50% scalp hair loss. Patient input was essential to the development of this content valid measure.
Report on the progress of NAAF’s Patient-Reported Outcome (PRO) Consortium to develop a single, consensus-defined PRO instrument that can be shared across industry partners and other ongoing initiatives to incorporate the voice of the patient in alopecia areata research.
Bruce Patsner is an Oncologist and has served as Director of North American Operations for Legacy Healthcare since 2017; he is based in Boston, Massachusetts.
More from National Alopecia Areata Foundation (20)
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
1. MEETING SUMMARY
November 14-15, 2016
ALOPECIA AREATA RESEARCH SUMMIT
Building & Crossing the Translational Bridge
New York City · New York · USA
2. Opening Session
Bill Ju: Building the Ecosystem for Research Translation
• Identify the problems worth solving – novel diseases/targets
• Need a deep understanding of the biology/investigators
• Importance of both basic and clinical researchers
• Understand the clinical outcome assessments and measures
• No market data in AA – must be overcome to establish $$ model
• Must have IP protection – what is the asset?
• Ecosystem building – interest from the business community
• Success stories – small companies that engage in the ecosystem early to get advice,
guidance, access to early funds for pilot studies; role of catalysts such as Advancing
Innovation in Dermatology.
22016 AA Research Summit
3. Session 1 - Setting the Stage & Raising the Bar
Maria Hordinsky: Clinical Update in AA
The Clinic Visit in 2016 – patients are armed with information! Discussion of new treatment options
such as JAK inhibitors are no longer ‘emerging’ they have emerged! Still many clinical unsolved
mysteries, such as patchy persistent disease. More work to be done to test efficacy of new agents in
placebo-controlled trials. Lots of new questions to be answered!
David Norris: Overview of Past NAAF Research Summits
Five Research Summits up to now: 2008, 2009, 2010, 2012, 2014. First summit 2008 in Bethesda.
Genetics and Immunology…repurposing of autoimmune drugs was the goal. Second summit 2009 in
Denver focused on Immunology, animal models, drugs used in other diseases. Third summit in 2010 in
NYC, was focused on demand of new treatments by AA patients. What tools were needed to foster
clinical research – tools, biomarkers, outcome measures. Fourth summit in 2012 – focused on
consolidating the mechanisms recently uncovered in AA and how these could be targeted by modern
therapies used in other diseases. Fifth summit in 2014 – New drugs showing promising results in AA.
Larger meeting with 90 participants, focus on new technologies and directions, new tools. Development
of core uniform protocol. Sixth summit in 2016 – here we are! Advanced understanding of genetics and
immunology, new animal models, epidemiology, QOL, translational research opportunities. First Summit
to have participation of Industry partners! Welcome everyone!
32016 AA Research Summit
4. Session 1 (Continued)
Angela Christiano: Update on Genetics and Immunology
GWAS studies have provided at least 14 genes involved in AA, with more to be discovered if GWAS
studies can be expanded. Immunological studies have focused on the role of CD8+ T cells in mediating
disease, and the use of JAK inhibitors to prevent and treat AA in the C3H/H3J mouse model. These
preclinical studies paved the way for early clinical investigation in patients, which has been done in
several centers to date. Gene expression Studies have uncovered biomarker signatures that can be used
to follow response to treatment. Goals for the coming year include investigation of new pathways,
including autophagy, pigmentation and ‘stress’ pathways in the hair follicle. Environmental factors such
as the microbiome are also under study in patients with AA.
42016 AA Research Summit
5. Session 1 (Continued)
5
Ralf Paus: Revising the Immune Privilege Hypothesis
Overview of the concepts of IP and how they relate to AA. New physiological role of gamma delta T
cells – to scout for stressed HF signals and sentinel cells that then kick off the immune cascade. New
immune cell types were discussed including Langerhans cells, Mast cells, gamma delta T cells among
others. The need to understand these cell types as well as Tregs, NK Tregs and additional cytokine
pathways and mechanisms still need to be discovered. As a step toward a truly ‘curative’ therapy would
involve restoration of peripheral tolerance – multimodal therapies may be needed!
Madeleine Duvic: Update on AA Registry
There are 11,180 AA patients now registered. Of those, 8528 were diagnosed by a dermatologist. All
subtypes of AA are represented: AU 2617; AT 1088; AAP 2422; AAT 2401. All ethnic/racial groups
represented. The registry has supplied DNA, serum, samples to enable wide range of studies. There are
6000 patients that have not yet been sampled, this needs to happen! Importantly, many Registry
patients have overwhelmingly consented to be re-contacted for participation clinical trials.
2016 AA Research Summit
6. Lunchtime Keynote
Yaron Tomer: Autoimmune Thyroid Disease
• Th1 vs Th2 in the thyroid gland. Th1 – apoptosis in Hashimoto’s hypothyroidism;
versus Th2 – hyperthyroidism in Graves
• Shared genes with AA, Graves and Hashimoto’s
• Most genes participate in antigen presentation (CD40, HLA, PTPN22, Thyroglobulin,
TSHR, CTLA4) hence the focus on small molecule targeting
• HLA DRB1 must have Arginine 74 to predispose to AITD. Glutamine 74 is protective
• Interaction studies of Thyroglobulin and HLADR AA 74 – synergistic not adaptive
• Hypothesis; the Arg pocket enables presentation of thyroid autoimmunity antigens
• Screen of small molecules that block binding of peptide to the A74 binding pocket
• Registry has supplied DA, serum, samples to enable wide range of studies
• Three small molecules were positive; one of them was in the compound library
• In vitro validation using humanized mouse molecule (Li CW, et al., 2016)
• Cepharanthine is the S53 compound from Stephania cepharantha Hayata plant;
natural alkaloid (Rogosnitzky M and Danks R, 2011/Tabata et al, 2012)
• Looking now into human clinical studies to take place in the US
62016 AA Research Summit Adapted from Abbas, Cellular and Molecular Immunology, 5th Edition
7. Session 2 - Tools of the Trade: Clinical Trial
Design & Outcome Measures
Elise Olsen: A new visual Aid for Assessing Hair Loss in AA
ALODEX score – Alopecia Density and Extent Score (JAAD, in press). Can track absolute hair loss, and
small changes in density that may otherwise go undetected with SALT score. Can do lesional scoring.
ALODEX and SALT cannot really be compared. But they tend to trend in the same direction. New valid
metric for hair loss in AA. Unique properties of ALODEX – determines % scalp hair loss vs % scalp
baldness. Only electronic capture. Instantaneous mathematical calculation. More time consuming.
Allows tracking of areas of baldness new and old.
72016 AA Research Summit
Leslie Castelo-Soccio: Using Computer Vision to Quantitate Pediatric AA
Measurements were developed for adult heads – not kids! Steps to developing a new tool: photo library
of more than 800 images that was used to develop new algorithm. Key collaboration with a computer
scientist to develop App!
8. Session 2 (Continued)
8
Tito Mendoza: Update on the Use of the AA Symptom Impact Scale
AASIS – AA Symptom Impact Scale is a 13 item questionnaire uses a 0-10 scale (10=worst). Data collected from
Registry (202 pts), plus new data (250 pts) = pooled data (total of 452 pts). Several pharma companies have asked
permission to use the AASIS in their clinical trials, some of whom are here. AASIS is free to use. New directions:
cognitive debriefing to identify minimum age of participants who can take the AASIS. Currently it is 18 yrs. old.
One pharma company has expressed interest in pediatric instrument. Validation is an iterative process; Tito would
appreciate if industry can share their results.
Amy Paller: Pediatric Clinical Trial Design
Children are not just small adults! Recruitment is a greater challenge. Parental consent is time consuming. More
intense requirements by IRB – invasive tests for trials. Assent for older kids. Greater fears in peds population for
safety. Children are less cooperative than adults. Difficulty in scheduling visits (during school, work hours). More
time required for every visit – blood, biopsies. How to minimize the number of visits/missed school and work.
Outcome measures – SALT for children, CDLQI validated in children, but is not specific for AA. Need a validated
and specific instrument for peds. Intervention studies are desperately needed for AA in kids. Topical studies would
be welcome!
Joel Gelfand: Clinical Trials, Epidemiology and Biostatistics in Skin Diseases
Epidemiology considerations – get help early in study design! To call the statistician after the experiment is done
is a post-mortem analysis! Ask a well formulated study question. Define exposure, outcomes, confounding factors.
Minimize selection and information bias. Plan for statistical error. Develop an analysis plan. Overview of different
type of study designs: cross-sectional, population-based, cohort studies, case control studies. Interesting statistic:
What percent of observational studies of treatment effect are confirmed by RCTs? 10% confirmation rate of
preclinical studies (such as in mice). 75% confirmation rate of observational research (open label pilot studies) in
patients. Concept of Equipoise – weighing the benefit versus risk.
2016 AA Research Summit
9. Session 3 - Success Stories: Lessons from
Clinical Studies with JAK Inhibitors
92016 AA Research Summit
Julian Mackay-Wiggan: Update on Clinical Research in AA
Ruxolitinib study – 12 patients, 20mg BID. Regrowth as early as 4 weeks. 9 of 12 had 50% regrowth.8 of 9
achieved their endpoint by week 12 (75% response rate). Tofacitinib study – 12 patients 5mg BID up to
10mg BID. Followed for 6 months. 7 of 12 had 50% regrowth. 6 of 7 responders needed dose escalation
(approx. 65% response rate). Relapse 4-8 weeks after stopping. Abatacept study – one complete responder
out of 15 treated – continued to regrow even after end of treatment. Biomarker analysis using gene
expression performed in all studies.
Wilma Bergfeld: Cleveland Clinic AA Tofacitinib Results
Open retrospective study. Moderate to severe, recalcitrant patients, some with RA and AA. Thirteen
patients, all recalcitrant to other therapies. Average regrowth at 4 months, some as late as 9 months .
Some are on drug for 18 months. One AU patient was African American, regrew his eyebrows and lashes
but not scalp and not body hair. Three patients had total regrowth. One was duration of 30 yrs. Response
rate = approx. 54%.
Justin Ko: Oral Tofa in Severe AA – Stanford/Yale Study
All patients are on 5mg BID and for 3 months duration only. Enrolled 70 patients – 66 finished study. Long
durations 1-43 years; average 5 years duration. ¾ were AU/AT patients. Biomarker analysis using gene
expression studies. Outside the study – treating approx. 80 patients. About 2/3 of patients grow clinically
acceptable patients at 6 months or longer. Roughly 66% overall response rate.
10. Session 3 (Continued)
10
Brett King: Tofa in AA in Adults and Adolescents
Approx. 90 adult patients treated and 13 adolescents with tofa alone or tofa with pulse steroid. Overall
response rate approx. 60% in adults, 75% in teenagers. Patients with disease duration less than 11 years
have better responses. Relapses seen while on treatment, and after drug stopped. Topical studies
treating one patient with compounded ruxo, regrow brows. Three compounded tofa formulations, no
positive results.
Elise Olsen: Topical INCB018424 in AA in Open-label Treatment Period (Abstract #006)
Study evaluated topical ruxo 1.5% cream in AA patients. Part A: open label 24 week study in 12 subjects.
18-70 years of age. Current episode of either 6 months 50-99% loss, or 12 months 25-50% loss. Exclusion
of AT AU or ophiasis. 6 of 12 patients (approx. 50% response rate) reached SALT50 response at end of 24
weeks. Promising data to encourage further development of topical JAKs.
Alice Gottlieb: Topical JAK Inhibitors in Psoriasis
Lessons and cautions from topical psoriasis JAK inhibitor studies. These were published early in 2011-2012
but no further development. Why? Systemic absorption? Biopsies limit accrual. Get early formulation
data, assess systemic exposure with penetration enhancers, and put biomarker studies into subtotal
inunction studies, so that accrual moves faster. Submitted paper on vitiligo, and JAK inhibitors may be
useful for lupus, dermatomyositis and others.
2016 AA Research Summit
11. Session 3 (Continued)
11
Take Home Lessons from Combined Studies
• Relapse seen in all studies after treatment; sometimes worse than baseline, starting 4-8 weeks after stopping drug.
• Flares observed while on treatment in several studies, sometimes in different pattern (ophiasis) than original AA (12% in Yale
study, 4 pts Stanford, 1 pt. Columbia).
• African American individuals in non-responder groups (though also in responder groups).
• Ruxo treated patients regrowth visible earlier than tofa treated patients. Tofa required dose escalation in all studies, longer
treatment periods.
• Each study had responses in patients with long durations of disease; however, two studies suggested that less than10 years
duration had better responses; one study suggested shorter duration of current episode correlated with better responses.
• Regional differences in regrowth: Eyebrows, lashes and body and facial hair don’t correspond to scalp hair. Patients respond
differently on different body sites.
• One study (Yale) added pulse prednisone 300mg Q4 weeks for 3 doses, in addition to elevated dose of tofa to improve
responses. Comment by Dr. Shapiro that he has combined oral tofa with ILK and seen faster responses to tofa.
• Two studies (Stanford/Yale and Columbia) conducted gene expression biomarker analysis.
• No study reported improvement in AGA hair loss in patients taking JAK inhibitors. Perhaps not surprising; this may require
topical administration.
• AE: generally mild. Acne (8% in Yale study); trace hematuria (Columbia), eczema herpeticum (Stanford); LFT, lipid
abnormality (Cleveland), URIs.
Despite widely heterogeneous groups of patients, durations of disease, different dosing regimens, and length of
treatment, response rates were highly consistent across sites (range 50-75%):
Columbia: Response to oral ruxo = 75%, oral tofa = 65%.
Cleveland: Response rate =approx. 54% oral tofa.
Stanford: 66% overall response rate oral tofa.
Yale: approx. response rate 60% in adults, 75% in adolescents for oral tofa.
Duke/Incyte: approx. response rate 50% for topical ruxo.
2016 AA Research Summit
12. Session 4 - Emerging Technologies & Targets
122016 AA Research Summit
Ali Jabbari: Biomarkers for AA and Clinical Trials
AA Gene expression biomarker led to development of ALADIN – AA Disease Activity Index. Ruxolitinib trial
– responders had high scores at baseline that normalized on treatment, and non-responders did not.
Tofacitinib trial – responders at baseline had high scores, and normalized on treatment, albeit at different
dosages. ALADIN may distinguish responders from non-responders at early treatment time points, after
treatment, to predict who will and won’t respond and on what dosages.
Zhenpeng Dai: AA Reversal by IL7R Blockade via Upregulation of PD-1
IL7 is a gamma chain cytokine that is dysregulated in AA in humans as well as C3H-HeJ mice. Investigation
of its potential utility in prevention and treatment of AA in C3H/HeJ mice. Unlike the other antibodies
tested, blockade of IL7R can reverse early onset AA in mice, potentially via PD-1 pathway. Potential new
therapeutic target for AA.
Amos Gilhar: Non-conventional T-cells in the Pathogenesis of AA
NKG2D is expressed on other cells than CD8 T cells, such as ILCs. Incubation of ILC1 with hair follicles.
More catagen follicles in ILC1 co cultured cells and human hair follicles. iNKT cells are present in AA lesions.
Used humanized mouse AA model. Alpha-GalCer induced expansion of NKT10 cells. Alpha-GalCer
prevented development of AA in the humanized biopsy model.
13. Session 4 (Continued)
13
Pantelis Rompolas: HF Regeneration and Pathophysiology Live Imaging
Mouse model of stem cell dynamics. Live imaging of mice. Ability to follow individual hair follicles
during regeneration process. Mechanisms of hair growth – is a niche required? Is DP required? Ablation
of epithelial stem cells does not prevent regeneration – it can readily recover after damage and
continue with HF growth. Dermal input is absolutely required. Epidermal niche not required. Non-HF
epithelial cells can enter the niche and acquire a HF fate. Clearance of catagen debris does not appear
to occur via immune cells.
Jerry Shapiro: Hype or Hope? Data Review of Microneedling and PRP
Blood is 45% cells, and 55% plasma. 0.15 of cells are platelets. Plasma has lots of good nutrients that
could support hair growth. Platelets have a lot of growth factors contained in platelets. Some are PDGF,
IGF-1, FGF, EGF, VEGF etc may help create a better environment for hair to grow. Need to get rid of
RBCs, and WBCs, inflammation, toxicity, etc. Only the Platelets are desired – plus the plasma. Can be
done from a blood sample that is spun in the office in front of the patient, they can see the centrifuge
to be sure they get their own cells back! One study of PRP in AA, half head study from Rinaldi et al.
Three groups – PRP, ILK, placebo. 3 treatments 1x monthly. One lesion was injected. 60% of patients
showed regrowth. Microneedling. 1.5-2mm needle depth. Mechanism of action – poor man’s PRP?
Angiogenesis? Breach of stratum corneum. Use a SkinPen device to make the needle holes.
Microneedling study in AA showed no improvement in 3-4 months. Roller needle device went 0.5mm in
depth, painful. After 3 months, 8 of 15 showed response, 12 of 15 after 6 months. No relapse. How
does it work – perhaps factors stimulated with wounding – VEGF, wnt3a and wnt3b.
2016 AA Research Summit
14. Dinner Keynotes
142016 AA Research Summit
Angela Rodgers: What Treatment Means to Patients
No safe, affordable, accessible treatment for AA is a problem. Skin, as a tangible and visible part of
the body, can have a magnificent effect on psychological status which is continuously involved in
socialization processes from childhood to adulthood (Shahin, A. et al., 2014). Increased prevalence
of mental health issues in the alopecia areata community. Developing a breakthrough treatment for
those with AA would be good for combating the disease but also restore the mental health of the
community.
Eleanor Perfetto: Activating the Patient Voice in Drug Development
Patients are experts on their disease. PDUFA VI guidance to solidify patient engagement in burden of
disease, holistic sets of impacts, measures for identified impacts, and clinical outcomes assessments.
The goal is active engagement over passive study enrollment. Studies that are patient-directed or in
partnership with patients offer the most active participation.
15. 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. Session 6 – Introduction & Review
162016 AA Research Summit
David Norris: Review and Summary of Day One Discussions
Spectacular progress in genetics and immunology to understand mechanisms of AA. Development of AA
translational research program: biobank, uniform trial platform including biomarkers, extensive clinical
material and investigators.
Positive feedback loop in AA
Divito & Kupper, Nature Medicine 20, 989–990 (2014).
17. Session7-WhatLiesBeneath:ElusiveAAAuto-Antigens
172016 AA Research Summit
Chris Nagao: Regulation of Skin Immunity by the Hair Follicle
Hair follicle keratinocyte-derived cytokines (such as IL7 and IL15) maintain resident memory T cells in the
HF. Both CD4 and CD8 Trm reside in the HF. ADAM10 ablation model leads to patchy hair loss with
exclamation point hairs. See infiltration of mainly CD4+ T cells and DCs in the isthmus and bulb area, which
happens first, and then disrupts HF morphology. Loss of HF immune privilege, measured by CD200
decrease, and increase of ICAM1 in ablated mice. Differential sensitivity to IFN among HF keratinocyte
populations and breakdown of IP and/or enhanced leukocyte recruitments.
Marta Bertolini: Identification of Antigenic Mimotopes in
AA Specific CD8+ T cells
Isolation of CD8+ T cells in AA and TCR sequencing. Take T
cells from lesional skin around the HF. RT-PCR to clone the
Beta chain, and then alpha chain in four patients with
different HLA types, several Vbeta clonotypes that differ
and vary greatly between AA patients. Eventually, screening
a peptide library with TCRs to identify antigens, which can
facilitate immunotherapy to eliminate pathogenic T cells.
Hou et al., Genes and Immunity, 2016
18. Session 7 (Continued)
18
Annemieke de Jong: Identifying Pathogenic TCRs in AA
TCR repertoire sequencing revealed that in the AA graft model, the skin graft carries with it a number of
T cells, which are then expanded in the recipient to generate a new repertoire which contains some
donor cells, but mainly these cells are newly primed T cells that do not overlap with grafted repertoire.
In humans, in lesional skin, there are many CD4 cells in some patients, CD8 in others. Compared to
blood, which are primarily CD8. These CD4 cells are comprised both of Tregs as well as non-Tregs; AU
patients may have less Tregs. Increase in clonality in AU compared to normal scalp. Several TCRs similar
in lesional skin and support antigenic drive.
2016 AA Research Summit
Alessandro Sette: Epitope Identification Screening in AA
Large scale screening for antigen discovery –
complementary to the two previous talks which were
very specific and focused on HF cells. Starting material is
rate-limiting. Collected 18 AA patients to donate a pint of
blood and collected PMBCs to be used in this screen. HLA
typing done in this cohort and 13 of 18 have A-0201
allele. Total of 311 peptides have been predicted, now
will be synthesized and conduct large scale screen!
Schulten et al. PNAS 2013
19. Session 7 (Continued)
192016 AA Research Summit
Teresa DiLorenzo: Similarities Between T1D and AA
T1D and AA have many similarities – infiltrates, ‘patchy’ disease – some islets have B cells that are
destroyed, others are intact. Similar prevalence of 0.15 for AA and 0.19 for T1D. No female to male
gender bias. Incidence of T1D is increasing, maybe AA too in AA from Olmsted study. Environmental
factors – microbes, food, pollutants? Shared genetics – increased T1D in relatives of AA patients. BMC
Medicine 2013. Comorbid – vitiligo, psoriasis, AITD in both AA and T1D families. Many T1D and AA
genes are associated with general immune function. There are also susceptibility genes expressed in the
target organ (in Beta cells in T1D, and in AA HF cells). CD8 as well as CD4 cells important in both. Models
of Human TCR transfer into NOD.scid mice – may be useful for us in the future.
13 Y.O. with type 1 diabetes for 5 years
Diabetes (2016) 65:719
20. Session 8 - Just Skin Deep: Immunology of the Skin
202016 AA Research Summit
Dan Kaplan: T cells, DCs Autoimmunity and the Hair Follicle
Signals that recruit and keep immune cells in the skin. Adult human Langerhans cells require TGFß for
epidermal residence – autocrine loop. LCs secrete and require TGFß. In epidermis, only two factors activate
latent TGFb – avB6 (required for LC residence) and avB8 integrins. In bulge, LC are excluded; in isthmus, LC
are included. avB8 is expressed in the isthmus, whereas avB6 is in the interfollicular epidermis (patterned
with respect to integrin localization). Loss of TGFb is required for UV-induced LC migration. UV reduces
integrin expression in epidermis, What about Tfm cells? Same mechanism exists for Trm; maybe
generalizable for other epithelia, such as intestine. Application to AA – targeting TGFB or its activation
could be used to deplete Trm from epidermis.
Michael Rosenblum: Tregs in Skin and HF Stem Cell Differentiation
Traditional role of Tregs – suppressing inflammation. Non-traditional functions –
glucose metabolism, muscle repair, lung epithelium repair after injury. Do they also
have a similar specialized function in skin? Tregs are active around mouse hair follicle,
send appendages into HF milieu for sampling environment. In human HF, same thing,
Tregs cluster around HF. Depilated mice in telogen with Treg depletion fail to enter
the next anagen. Treg are required for bulge HF stem cell activation/proliferation (not
seen in other KC populations) as well as KC differentiation during anagen induction.
Mechanism: Treg expression of JAG1, a notch ligand, and expression of Notch target
genes in HFKCs. Targeting of JAG1 in Tregs and depilation attenuates anagen entry,
failure of Notch dependent differentiation in HFKCs. AA GWAS genes reflect Treg
genes (Eos, IL2, IL2RA) and low-IL2 clinical study may reflect influence on Tregs in hair
regeneration function as well as immune responses.
21. Session 8 (Continued)
212016 AA Research Summit
Niroshana Anandasabapathy: Making and Breaking Tolerance
Tissue DCs in skin in epidermis and around HF. Tissue factors (nurture) may override nurture (ontogeny
or origin) of immune cells. Skin DC subsets contain 23 cancer IO targets. Many of these are in NFkB
pathway. Do monocytes and macrophages also share this signature? Yes – same signature in the skin.
Signature is conserved in mouse and human, conserved upon skin entry, and shared across
monophagocytes. Most highly differentially expressed gene – SOCS2. Loss of SOCS2 reveals novel IO
target in cancer, and expanded immune priming and adaptive anti-tumor immunity. How does this link
to disease states? Single cell sequencing in human melanoma metastasis and other diseases states. Trm
cells and DC cells are relatively under-studied populations in AA, may represent areas for future
research.
Michel Gilliet: Commensal Bacteria Control pDC Recruitment in Skin
pDCs accumulate in the dermis in early psoriasis lesions and production of IFN1 triggers cascade leading
to full disease expression, upstream of TNFa, IL23, IL17 and IL22. What activates pDCs? Antimicrobial
peptides in the skin not expressed in healthy skin, but are upregulated in wound healing and
mechanical stress and injury. Complexes of AMPs and DNA enter via pDCs to initiate immune processes
leading to psoriatic plaque. In AA, reported elevation of IFNa and pDCs (2016 reference). Is the Koebner
phenomenon as a shared feature? Tape stripping recruits pDC to skin in humans and skin wounding in
mice. Interestingly, skin microbiota are required for pDC activation in injured skin. AMPs kill bacteria,
bind to bacterial DNA and lead to inflammation and wound healing. In humans, microbiota depletion
decreases IFNa.
22. Session 9 - Genes, the Hair Follicle
& the Microenvironment
222016 AA Research Summit
George Cotsarelis: Nutritional Factors Influencing Alopecia
Micronutrients create optimum conditions for hair shaft formation – Vitamin D, Zinc, Iron.
Is telogen effluvium a trigger for AA? TE pushes anagen follicles into telogen prematurely (dysregulated
catagen?), commonly due to fever, medications, malnutrition. If catagen goes awry, can this precipitate AA,
expose antigens? Examples – hairless, VDR mutations cause dysregulated catagen, also interact with
thyroid hormone receptor. Does low iron decrease the threshold for developing AA? Hair phenotypes Iron
deficient mouse models, appear to have abnormal catagen. Iron related genes, there are many in the hair
follicle. Could micronutrient deficiencies contribute to non-responders to AA therapies?
Michael Rendl: Niche Control of HF Formation and Regeneration
Hair-GEL.net is a resource to catalogue hair genes from at least 7 different cell populations in HF
morphogenesis. Recently updated, 14 different cell types in adult HF. Searchable database for candidate AA
genes/antigens to see where they are localized in the HF. Now working on hair regeneration wave profiling.
Sennett et al, Developmental Cell 2015
23. Session 9 (Continued)
232016 AA Research Summit
Natasha Botchkareva: Role of miRNAs in AA
Comparison of miRNAs in C3H affected vs unaffected skin. The downregulation of miR- 486 and -451 in
AA-affected mouse skin suggests their putative role in prevention of the collapse of hair follicle immune
privilege in normal anagen hair follicles. Possible roles in inflammation or apoptosis. Treated AA mice
with miRNA mimics and saw reduction in CD4+ and CD8+Tcells; do they delay AA onset. Mir486 is
expressed in human HF (but not mir451). Organ culture assay treated with mir486 upregulates MHCI,
HLA, etc. Downstream targets not yet known – CADM1, FGF9, SP5. Overexpression of CADM1 can cause
AA (Fiona Watt lab, JI, 2012).
Tiffany Scharschmidt: Commensal Microbes and HF Morphogenesis Drive Treg Migration into Skin
A wave of Tregs into neonatal skin mediates tolerance to commensals; Tregs are required for this (p6-
13). HF morphogenesis directs Tregs into skin. Commensals are required for this process to occur.
Search for: chemokines expressed in HF x receptors on Tregs at same time points. Identified one
pathway involved: CCL20 and CCR6. CCL20 expressed near isthmus, and CCR6 expressed in skin Tregs.
CCL20 preferentially drives neonatal Tregs into skin in vitro. CCR6 promotes Treg accumulation in skin.
Anastasia Khvorova: RNA Chemistry toward Modulation of Gene Expression in Skin
Delivery much improved with targeting molecules attached to siRNA to get into cells. Recent paper in
NEJM shows one-year knockdown of target with single subQ injection. Field has matured enough to
target any gene in skin – delivery easier than many other tissues.
24. Session 10 - Understanding the Commonalities
Across Autoimmune Diseases
242016 AA Research Summit
Lynn Petukhova: Comorbidities in the AA Registry
Identifying disease subtypes and mechanisms and overlaps in genes and phenotypes. Using EHR data to
identify comorbidities among AA patients (showed T1D, RA, Ps, Lupus, others) in one study from Columbia
as well as a Danish health study. PheWAS studies – a cohort that has been GWAS analyzed and compared
to EHR data. AA SNPs are represented in 275 different conditions, including autoimmune, inflammatory,
cancer, and behavioral disorders.
John Harris: Understanding Parallels between
Vitiligo and AA
Both vitiligo and AA are mediated thru IFNg
pathway, but treated differently. Location of
the inflammation is what differs, not the
infiltrate itself. Systemic drugs should work in
both. Vitiligo has prominent IFNg signature but
few psoriasis pathway cytokines. Targeting
JAK1/2 using tofa and ruxo can reverse vitiligo
in mouse model. Two case reports –one tofa,
and one ruxo in human patients. Levels of
CXCL10 dropped when patient started ruxo,
showing drug hits target IFNg pathway.
25. Session 10 (Continued)
252016 AA Research Summit
Emma Guttman: Cytokine Targeted Therapy: Lessons from AD and Other Diseases
Highest comorbidity for AA is AD (38%). Previous genetic study showing IL13 SNPS, and Th2 cytokines
and several other studies. Th2 axis picked up on RT-PCR not array studies, since they may be expressed
at low levels. Dupilumab study patient who had AD as well as AA. One patient with apremilast had
patchy regrowth. Three patients with ustekinumab, must be used at higher dose in AD than psoriasis.
Two other patients had regrowth of some hair. Higher inflammation at baseline was associated with
better clinical responses. Targeting AA with multiple drugs aimed at different pathways.
Brian Kim: Neuronal Type 2 Cytokine Signaling
Regulates Chronic Itch in AD
Itch is the most debilitating symptom of AD. IL31
secreted by Th2 cells stimulates sensory neurons
directly as a pruritogen. Do Th2 cytokines induce
itch? IL4R and IL13R expressed on dorsal root
ganglia. Deletion of IL4R on the DRG neurons led
to reduction in itch over time. Dupilumab leads to
reduction in itching in AD clinical trials. Additional
mechanism of action of this drug on sensory
neurons and central itch. Nerve bundles wrap
around HF, reminding us to think about common
mechanisms for AA.
26. Session 11 - Challenges and Opportunities:
Advancing Drugs to Patient Care
262016 AA Research Summit
Bozena Michniak-Kohn: Topical & Microneedle Drug Delivery
New methods for topical drug delivery. Two new approaches –
targeted delivery – microneedles and tyrospheres. Nano
formulation that can encapsulate cargo and deliver cargo
specifically to the hair follicles and upper epidermis.
Raphael Clynes – Inflammatory Biomarkers: Informing Clinical Trials
Can we borrow from immunological biomarkers being developed in the immuno-oncology field that
might be applicable to AA. Lessons from oncology that are applicable to autoimmunity – in reverse. New
ways to look at infiltrate (immunophenotyping CD8 cells, serum chemokines, TCR repertoire, Functional
markers in blood (pSTAT, IFN, CD107) as well as end organ (Immunoscore IHC, RNA profiling, TCR
repertoire, crawl-out studies, Immunophenotyping CD8 cells, RNAscope). Are drugs reducing clonality
of T cells in AA skin (for example).
Pharmaceutics 2015, 7, 90-105.
27. Session 11 (Continued)
272016 AA Research Summit
Antonella Tosti: Repurposing Drugs for AA - Vytorin
Investigation of statins in AA. Block IFNg and modulate JAK/stat pathway. Small study of 19 patients
with moderate AA. At 24 weeks, 14/19 patients responded. Stop treatment and 7 patients maintained
their hair. A second study was done on severe AA, 20 patients, treated for 24 weeks. One patient had a
clinical response with patchy regrowth. What about topical statins – Dr. Jimenez study on topical statins
in C3H-HeJ mice, restored hair growth. Can statins be utilized to prevent relapse (in mouse)? Heat
treatment to induce AA in C3H model (by cellular stress). Series of 42 patients with AA in practice,
added statin to their treatment regimen once they have regrown with another treatment. 30 patients
had severe AA (including ophiasis) and 12 AT/AU. After 6 months 31/42 patients had minimal or no
relapses. After 12 months, 11 of 31 patients had relapse when discontinued treatment. Statins may
have utility in helping to prevent relapse after response to other therapies. Patient reported muscle
pain as expected side effect.
Natasha Mesinkovska: Unconventional Therapies
Common questions: medications, lifestyle, devices. Use of Allegra antihistamines (fexofenadine) for
mast cells in AA. Perhaps useful in early AA. Ice caps for chemotherapy alopecia. Cryotherapy for AA
353 cases over 22 yrs. For Patchy AA, face and neck, children, adjunct to JAK inhibitors. Low-dose
naltrexone for autoimmune disorders. Opiate antagonist used for drug addiction. Case reports in other
autoimmune disorders and inflammatory alopecia's.
28. Session12-RegulatoryMatters&FundingOpportunities
282016 AA Research Summit
Dory Kranz: Patient-Focused Drug Development Initiative
Incorporating the voice of the patient in AA clinical research. Upcoming PFDDI meeting in FY2016-2017.
Great opportunity to make the case for AA to the FDA. Paper: AA is not a cosmetic disease. New initiative:
Patient-centered outcomes consortium, to create a single outcome measure that can be shared across
industry partners.
29. Session 12 (Continued)
292016 AA Research Summit
Devanand Jillapalli: FDA Orphan Drug Designation and Funding Opportunities
Orphan designation if a disease occurs in less than 200,000 individuals. Importantly, the subset must be
specifically tied into the use of the drug. Properties of the drug could involve: mechanism of action (i.e.:
antibody-specific or biomarker-based drug); or toxicity of the drug limits is use to refractory patients,
for example. Drug must be useful in the orphan subset, and not in the rest of the indication/patients.
Clinical Trial Grants Program – awarded $23M this year. Natural History Grant Program. $400kyr/5yrs.
See OPDD website for more information.
Ricardo Cibotti: NIAMS Funding Opportunities
Alopecia Areata is a quickly growing area of NIAMS research! In 2007, skin immunology and disease
program was created within NIAMS. Clinical trials grant program – many opportunities but need
partnership with drug companies to donate drugs for these grants!
Kara Odom Walker: PCORI - Engaging Patients in Clinical Trials and Outcomes Research
Comparative effectiveness research – phase 4 studies, real world assessments. Five areas focused on
healthcare. Funding deadline Jan 17 2017. Send inquiries prior to submission. PCORnet – big data
networks. Questions that can be answered in a real-world setting – questions important to patients,
caregivers, payers. Information that can be disseminated and implemented in the future.
30. NAAF SUMMIT 2016 - WE DID IT!!
On behalf of NAAF and Co-Chairs, Drs. Maria
Hordinsky, Angela Christiano and John Harris, we
thank you for your interest in alopecia areata, your
thoughtful participation in the Summit, and your
enthusiasm for the future of alopecia areata research.