Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation
Performance · Mean plasma progerinResult — go to the resultFold increase 95Authors' conclusion
A sensitive, quantitative immunoassay for progerin was developed and used to demonstrate high progerin levels in HGPS plasma that decreased with lonafarnib therapy. The extent of improved survival was associated with both the magnitude of progerin decrease and duration at lower levels.
Study context
- Population
- Patients with Hutchinson-Gilford progeria syndrome treated with farnesylation inhibitors (lonafarnib±pravastatin and zoledronate) at Boston Children's Hospital, and non-HGPS participants
- Participants
- 69 vs 74
- Comparison
- Plasma progerin in hutchinson-Gilford progeria syndrome (HGPS) vs non-HGPS; before vs during lonafarnib-based therapy
- Non-HGPSn = 69reference
- Drug-naive HGPSn = 74
- Outcome
- Plasma progerin quantity, response to progerin-targeted therapy, and relationship to survival
Methodological detailsimmunoassay development and clinical evaluation, cross-sectional non-HGPS cohort, longitudinal HGPS cohort, 3 sequential open-label clinical trials, prespecified performance parameters, joint modeling with time-dependent slopes
- Immunoassay development and clinical evaluation
- Cross-sectional non-HGPS cohort
- Longitudinal HGPS cohort
- 3 sequential open-label clinical trials
- Prespecified performance parameters
- Joint modeling with time-dependent slopes
Performance
Mean plasma progerin
Fold increase
95
P < 0.0001
By group
As reported in the abstract
- Progerin levels did not differ by sex
- P = 0.99
Further findings
Assay performance
- Dynamic detection range
- 59 to 30 000 pg/mL (R2=0.9987)
- No lamin A cross-reactivity
Progerin change with lonafarnib · within 4 months; up to 10 years
- Average per-visit progerin decrease from baseline
- 35% to 62% (all P<0.005)
- Effects not augmented by adding pravastatin and zoledronate
- Levels fell within 4 months and remained lower for up to 10 years
Progerin decrease and survival
- Magnitude of progerin decrease positively associated with survival
- P < 0.0001
- 15 000 pg/mL decrease yields decreased risk of death
- 63.9%
- For any given decrease, life expectancy increased with longer treatment duration
Original publication
Plasma Progerin in Patients With Hutchinson-Gilford Progeria Syndrome: Immunoassay Development and Clinical Evaluation. Circulation. Published 15 March 2023. doi:10.
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