Key Issues to Tackle to Build a Brighter Future for PCD Patients and Caregivers

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


To promote research, increase public awareness,

and provide information and support services for

individuals with inherited ciliary disorders and their

caregivers.

PCD Foundation (PCDF) Mission Statement


PCDF Organizational Structure


Where we are today:• Mailing list: 836 patients (self-identified) & family members• Contacts: 2057 including patients, family members, friends,

vendors, physicians, researchers, etc. • Method: Email, social networking, other electronic means• Membership: No official requirements or dues

Where we want to go:• A patient registry

– Based on actual diagnosis (not self-reported)– Automated vs. today’s manual data entry

• Expanded mailing list & contacts• Increased frequency of communication

PCDF Membership & Communications


PCDF Meetings

• 1 Annual Scheduled Meeting: Annual Family Event– Usually 2 days in the summer – Open to patients, family members, medical professionals &

others interested in PCD– Speakers are experts in PCD who interact with families– Strong focus on education, but we have fun, too– This year: 15-16 July in Atlanta, GA. You are welcome!!

• Ad hoc regional events (opportunistic)• Future Meeting Goals

– Regional Education & Support Events– Scientific Meetings: Had 1 in St. Louis– Online Meetings & Teleconferences


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!


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


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


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)


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


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


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


‘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


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


Develop Treatment Guidelines (US only?)

Path to Clinical TrialsRaise Awareness


Increase Research Collaboration: Ciliopathies

Create research roadmap based on shared priorities



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


• 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)

Key Issues to Tackle to Build a Brighter Future for PCD Patients and Caregivers

Health & Medicine

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