A76-29 A Longitudinal Study of Primary Ciliary Dyskinesia in Adults
K N Olivier, T W Ferkol, C Taylor, K M Sullivan, N Capps, K Zeman, W Jihong, W D Bennett, Y Z Lee, S H Donaldson, J Couch, J G Matthews, V M Daryani, S G Bradley, C Vo Buu, P Ryali, S D DavisAbstract
Rationale
Primary ciliary dyskinesia (PCD) is a rare genetic, progressively destructive pulmonary disease associated with impaired mucociliary clearance (MCC). However, validated, sensitive clinical trial outcomes for PCD are lacking. This natural history study was designed to assess functional and mucociliary clearance measures as potential endpoints for future clinical trials. Objectives: The primary objective of the study was to describe and characterize the inter- and intra-patient variability of physiological assessments in adults with PCD.
Methods
The PCD cohorts were planned to include adults who have a genetically confirmed diagnosis of PCD with 2 identified pathogenic/likely pathogenic variants within the following genetic/ultrastructural groups: DNAI1 ODA defect (n = 10), Other ODA defect (n = 10), IDA-MTD defect, CCDC39 or CCDC40 (n = 10), Radial Spoke defect (n = 10). These groups were selected to support the potential for inhaled mRNA therapy being developed for PCD. This longitudinal, observational study enrolled healthy volunteers (N = 6) and adults with confirmed PCD (N = 25). Using established, standardized approaches, spirometry and mucociliary clearance assessments were obtained at baseline and 1-month, with additional assessments performed at 6 and 12-months for some participants with PCD. The absolute and relative change from baseline in spirometry and mucociliary clearance were analyzed.
Measurements and Main Results
At both timepoints, baseline spirometry and mucociliary clearance values were greater in healthy volunteers compared to participants with PCD. Spirometry values varied within individual participants and between genotypes, reflecting the heterogeneous nature of the disease. In contrast, mucociliary clearance assessments showed less variability among individual participants with PCD with values near zero at each visit. There was virtually no difference between PCD genotypes.
Conclusions
In contrast to spirometry, mucociliary clearance measures are a repeatable measure, with consistently reduced clearance in participants with PCD, regardless of genotype, as expected based on disease pathophysiology. Thus, mucociliary clearance measurements may be a suitable endpoint for future clinical trials in testing disease-modifying therapies.
This abstract is funded by: ReCode Therapeutics