Identifies key challenges to overcome that will help people with primary ciliary dyskinesia (PCD) and other ciliopathies get the resources needed to improve the understanding of the disease, raise awareness about it, provide adequate and accessible treatments for it, improve diagnosis worldwide and ultimately greatly enhance the quality of life (and life span) of those affected by PCD.

1. PCD Support GroupInternational Conference on Inherited Disorders of Muco-Ciliary Clearance Primary Ciliary Dyskinesia Kartagener Syndrome Immotile Cilia Syndrome

2. Value of a Patient Group & a Global Coalition Support & Awareness Identify and support each other Establish a source of credible information for patients and caregivers Work with researchers, healthcare providers and other organizations to improve the lives of people with PCD and associated disorders Raise awareness among patients, healthcare professionals and the general public Advocacy Connecting with governmental / elected officials Advocate for access to treatments / research funding Research Help establish research priorities Provide a centralized, validated “pool” of patients interested in participating in research Funding Maximize potential and impact of dollars donated

3. Areas that Need Attention: Diagnosis PCD is frequently missed in those who do have it Ciliary biopsy ‘gold standard,’ but often poorly done High misdiagnosis (@30%) skew statistics & precludes PCD from clinical trials critical for treatment/cure research & dev Solution? A genetic test. For now? Unmask the Faces of PCD!

4. Areas that Need Attention: Misconceptions Fiction PCD is a mild, non-progressive disorder Consequences of PCD only affect older patients It is impossible to confirm the diagnosis of PCD Treatments already exist: They are the same as for cystic fibrosis (CF) PCD is incredibly rare and only affects a few thousand people Situs inversus is a benign condition ‘Normal’ life expectancy Fact Progressive disorder that can result in serious lung disease Infants can have severe lung disease; Neonatal mortality Centers of excellence, etc. can accurately diagnose PCD and CF are different genetic disorders. No PCD research to date. PCD is poorly understood and under-reported (Est. 400K WW) Not necessarily; Leads to delayed diagnosis Initial data indicates otherwise* What we need: Documentation of basic statistics to dispel these myths *See Appendix

5. Areas that Need Attention: Treatment Guidelines Creation & Use of Treatment Guidelines for PCD (in US) Standard of care varies dramatically from site to site Like diagnosis, treatment is driven by private insurance Reports of adults with no sputum or lung function tests No published guidelines = insufficient / no insurance coverage Unused guidelines = no benefit of published guidelines Access to Appropriate Care ‘Off-label’ drug use becoming a bigger problem TOBI (US$4,800/mo) & Cayston (US$5,200/mo) Average 3 calls/wk on this issue alone Adults with PCD have trouble finding pulmonologists familiar with disorders like PCD, CF and bronchiectasis Many adult CF pulmonary clinics will not see PCD patients

6. Goal: Accelerate development of/access to better therapies & cures How: Establish ‘Path to Clinical Trials’ to encourage pharmas to (co-) sponsor trials Why: Typical multi-center drug trials cost between US$2-40M What: Two key components include: Centers of Excellence* Provide diagnosis & treatment Center in every major city or at least in each state in the US *9 current sites: Participate in the GDMCC**, a clinical research network focusing on the PCD, CF, pseudohypoaldosteronism and other conditions related to mucociliary clearance A Registry Clinical, medical records-based database Ideally global, clinic-based, but may need to start with something regional, patient-driven Centers of Excellence to be conduit for PCD registry PCDF Proposed Solutions: Path to Clinical Trials **Genetic Disorders of Mucociliary Clearance Consortium (GDMCC)

7. Beyond PCD: PCD in the Larger Context Where we are today: Many patients do not understand value of current research efforts Results/purpose not clear Limited communication and collaboration between motile and non-motile ciliary researchers Researchers focus on their specific diseases Little perspective and joint effort at related to the grouping of the ciliary diseases We are missing opportunities to collectively understand the building blocks of diseases where cilia play a key role - and interplay b/t them Where we want to be: Immediate: Outline research in progress & where it ‘fits’ (i.e. goals for outcome, ultimate application - basic info vs. quality of life) Ideal: In a position to define & rollout a research roadmap based on shared priorities to study ciliary function & structure Joint efforts could push research forward faster and solve more problems for more people

8. PCD is a Ciliopathy: What’s That? A newly discovered class of diverse human genetic diseases arising from defects of ciliary function and/or structure *US Estimates

9. Brain Respiratory Reproductive Tract MOTILE (9+2) Embryo (Nodal cilium) MOTILE (9+0) “CILIUM” “Primary” (sensory) NON-MOTILE (9+0) Kidney tubule Bile duct Pancreatic duct Bone Cartilage Eye (Photoreceptor) *Fliegauf, 2007, Nat Rev Mol Cell Biol Ciliopathies Affect Many Organ Systems

10. ‘Ciliopathies’ Make PCD Important to More People Chronic obstructive pulmonary disease (COPD) 3rd leading cause of death in US* Affects 24M (US only), 12M diagnosed** Chronic bronchitis, emphysema, bronchiectasis Polycystic kidney disease (PKD) One of the most common life-threatening genetic diseases Affects over 600K (US only), 12.5M (Global) Fluid-filled cysts develop in the kidneys *Centers for Disease Control and Prevention (CDC), 2010; **COPD Foundation Heart Defects Congenital defects Heterotaxy Processes Related to Cilia Function: Onconogenesis & formation of tumors and cysts Skeletal & connective tissue formation Obesity Diabetes Why? They provide a way to better understand: Help for PCD could mean help for COPD, PKD and many other diseases

11. Summary & Next Steps Together, we can address these initiatives - and create a brighter future for PCD patients today & tomorrow . . .

15. 3.3% OtherRecent survey* on kidney disease in PCD patients & relatives *Very small sample size (only 33 respondents) and self-reported. Not meant to have scientific merit, but curious about potential to further investigate

17. 45.6 years (not including infants)*Very small sample size and self-reported. Not meant to have scientific merit, but curious about potential to further investigate