Product information and disease descriptionPlace of product in therapyApproaches to treatmentCurrent treatment options and standard of care
Limitations of current therapies
11 evidence topics · 20 sources
Summary
No approved therapy corrects the LAMP2 deficiency that causes Danon disease. The 2023 international consensus statement states that there are “no available therapies to specifically treat Danon disease”, that management rests on expert opinion and extrapolation from hypertrophic cardiomyopathy guidelines, and that no proof of efficacy exists for renin-angiotensin-aldosterone system inhibition or beta blockers in this disease. The sudden death risk models developed for hypertrophic cardiomyopathy have not been validated in Danon disease. Device therapy has documented failures: in a series of 7 participants, 1 died at age 12 from ventricular fibrillation that repeated defibrillator shocks did not terminate. GeneReviews advises caution with durable mechanical circulatory support because the disease involves both ventricles and states that ablation efficacy may be decreased.
Heart transplantation is the one intervention that sources credit with a survival benefit, and a minority of patients receive it: 30 of 116 participants (25.9%) in the International Danon Disease Registry, and 17.6% in a figure cited by a 2024 review. In a cohort of 38 recipients from 8 centers, the median age at transplantation was 20.2 years, 2 recipients died, 2 underwent retransplantation, estimated 5-year graft survival was 87.1% (95% CI 63.6% to 95.9%), and 7 episodes (19%) of grade 2 or 3 acute cellular rejection were reported. In a European registry, 5 of 8 male recipients of a transplant or an assist device (62%) died within 1 year of the procedure. In the OPTN/SRTR 2023 annual data report for the United States, pediatric waitlist mortality was 11.7 deaths per 100 patient-years, and 62 of the 733 pediatric candidates removed from the waiting list in 2023 (8.5%) died. Case reports after transplantation describe corticosteroid-associated skeletal muscle weakness, allograft vasculopathy that required retransplantation, and fatal thrombotic microangiopathy. The company developing RP-A501 describes transplantation as “not curative of the disorder in the long-term”, and registry authors advise transplant clinics to prepare for neuromuscular and psychiatric complications in the peri- and postoperative period.