1© Copyright 2011 | PCD Foundation | Confidential
Primary Ciliary DyskinesiaKartagener Syndrome
Immotile Cilia Syndrome
PCD Support GroupInternational Conference on Inherited Disorders of Muco-Ciliary Clearance
© Copyright 2011 | PCD Foundation | Confidential2
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
© Copyright 2011 | PCD Foundation | Confidential3
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!
© Copyright 2011 | PCD Foundation | Confidential4
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
Areas that Need Attention: Misconceptions
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
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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
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PCDF Proposed Solutions: Path to Clinical Trials
Goal: Accelerate development of/access to better therapies & curesHow: Establish ‘Path to Clinical Trials’ to encourage pharmas to (co-)
sponsor trialsWhy: Typical multi-center drug trials cost between US$2-40MWhat: 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 networkfocusing 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
**Genetic Disorders of Mucociliary Clearance Consortium (GDMCC)
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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 themWhere 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
Beyond PCD: PCD in the Larger Context
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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
Other Ciliopathies Incidence* Symptoms
Polycystic kidney disease (PKD)
600k Kidney cysts, renal failure
Joubert syndrome Unknown Hypotonia, mental retardation, breathing/vision issues
Meckel Grueber Unknown Polydactyly, brain herniation, sloping forehead, polycystic kidneys
Alstrom Unknown Cone-rod dystrophy, deafness, obesity, poly-dactyly, cardiomyopathy, metabolism syndrome
Usher 12k Retinitis pigmentosa, polydactyly, deafness
Bardet-Biedl Unknown Obesity, retinitis pigmentosa, deafness, developmental delays, polydactyly
© Copyright 2011 | PCD Foundation | Confidential9
Brain Respiratory Reproductive Tract
MOTILE(9+2)
NON-MOTILE(9+0)
“CILIUM” MOTILE(9+0)
Embryo(Nodalcilium)
Kidneytubule
Bileduct
Pancreaticduct
BoneCartilage
Eye(Photoreceptor)
“Primary”(sensory)
*Fliegauf, 2007, Nat Rev Mol Cell Biol
Ciliopathies Affect Many Organ Systems
© Copyright 2011 | PCD Foundation | Confidential10
‘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 PCDcould mean helpfor COPD, PKD
and many otherdiseases
© Copyright 2011 | PCD Foundation | Confidential11
Together, we can address these initiatives - and create a brighter future for PCD patients today & tomorrow . . .
Summary & Next Steps
Initiative Solutions Next Steps
Improve Diagnosis Path to Clinical TrialsRaise AwarenessGenetic Test*
Input & ideas welcome!
Combat Misconceptions Path to Clinical TrialsRaise Awareness
Input & ideas welcome!
Develop Treatment Guidelines (US only?)
Path to Clinical TrialsRaise Awareness
Input & ideas welcome!
Increase Research Collaboration: Ciliopathies
Create research roadmap based on shared priorities
Input & ideas welcome!
© Copyright 2011 | PCD Foundation | Confidential12
Overall: • 57% No kidney disease• 33% Kidney disease in
patient or blood relative
Of those 33%: • 33% Medullary sponge
kidney• 33% Small, malformed or
under-developed kidneys• 30% Polycystic kidney
disease (PKD)• 3.3% Other
• Recent survey* on kidney disease in PCD patients & relatives
Appendix: Kidney Disease Survey
*Very small sample size (only 33 respondents) and self-reported. Not meant to have scientific merit, but curious about potential to further investigate
© Copyright 2011 | PCD Foundation | Confidential13
• Survey* on life expectancy in PCD patients & relatives
Appendix: Life Expectancy Survey
*Very small sample size and self-reported. Not meant to have scientific merit, but curious about potential to further investigate
Age Gender Situs
0 M SI
0 F SA
0 F SA
0 M SA
24 F SA
24 M SS
39 F SI
42 M SS
45 F SI
47 M SS
50 F SI
55 F SS
64 M SA
66 F SS
Literature still says ‘normal life expectancy,’ but informal mortality data suggests this is not always the case. This misperception leads to a dismissive attitude about PCD in the medical community.
We are hearing more and more reports of neonatal mortality, often even when PCD is suspected, due to dismissing the seriousness of PCD-related complications.
Average age at death from this small sample survey:
• 32.6 years (includes infants)
• 45.6 years (not including infants)
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