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The study aimed to develop a plasma progerin assay to evaluate progerin’s quantity, response to progerin-targeted therapy, and its relationship to patient survival in patients with Hutchinson-Gilford progeria syndrome (HGPS), an ultrarare, fatal, premature aging disease caused by a toxic protein called progerin. The assay was developed with prespecified performance parameters, and progerin levels were measured in non-HGPS participants and drug-naive participants with HGPS who received lonafarnib treatment within 3 sequential open-label clinical trials. The results showed that the assay detected high progerin levels in HGPS plasma that decreased with lonafarnib therapy. The magnitude of progerin decrease positively associated with patient survival, and plasma progerin was identified as a biomarker for HGPS whose reduction enables short- and long-term assessment of progerin-targeted treatment efficacy.
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