Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic
hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO) …

Objective To determine whether preventive trials in genetic prion disease could be designed
to follow presymptomatic mutation carriers to onset of disease. Methods We assembled age …

Phenotypic screening has yielded small-molecule inhibitors of prion replication that are
effective in vivo against certain prion strains but not others. Here, we sought to test the small …

Context To date, penetrance figures for medullary thyroid cancer (MTC) for variants in
rearranged during transfection (RET) have been estimated from families ascertained …

Germline SDHA mutations are reported in a minority of pheochromocytoma/paraganglioma
(PPGL) cases but are associated with an increased risk of malignancy, leading some to …

Proline-rich transmembrane protein 2 (PRRT2) is the leading cause of paroxysmal
kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), and infantile …

Therapies currently in preclinical development for prion disease seek to lower prion protein
(PrP) expression in the brain. Trials of such therapies are likely to rely on quantification of …

Patients with pathogenic truncating mutations in the prion gene (PRNP) usually present with
prolonged disease courses with severe neurofibrillary tangle and cerebral amyloidosis …

Context Genetic testing is increasingly used for clinical diagnosis, although variant
interpretation presents a major challenge because of high background rates of rare coding …

Lowering expression of prion protein (PrP) is a well-validated therapeutic strategy in prion
disease, but additional modalities are urgently needed. In other diseases, small molecules …