Lay Summary of "TTR Gene Silencing Therapy in Post Liver Transplant Hereditary ATTR Amyloidosis Patients"

This is an article that was recently published in the journal "Amyloid" (June 2020). Researchers from different amyloid clinics across the US reported on their experience treating patients with hATTR amyloidosis, who already underwent liver transplant, with TTR "knock down" therapy.

The rationale is as follows:

1) some people with hATTR who undergo liver transplant continue to have disease progression, despite the fact that they have a "new" liver which does not have a mutated TTR gene;

2) One of the explanations behind the progression of disease after liver transplant is that wild type TTR (non-mutated TTR) continues to misfold and attach to the amyloid that was deposited prior to the transplant;

3) Decreasing the production of TTR protein should, in theory, slow down the deposition of misfolded TTR protein and the progression of amyloid.

Based on these observations, patients with hATTR who underwent liver transplant but continue to have disease progression were started on "TTR knock down" therapy.

The authors included 9 patients in total. All patients were started on Inotersen because the drug was available through a special program which allowed inclusion of patients who already had organ transplant. One patient later switched to patisiran. The median age was 61 years. The median time from liver transplant to initiation of TTR gene silencing therapy was 7.5 years. The median duration of therapy was 12 months. The neuropathy remained stable or improved in all patients. Five patients stopped treatment: 3 because of drop in platelet count, 2 because of reversible liver rejection. Three patients who discontinued treatment subsequently experienced worsening of their neuropathy.

The authors concluded that TTR gene silencing therapy in hATTR patients who underwent liver transplant but continue to have disease progression, could be a treatment option. However, one needs to monitor the renal, liver and bone marrow functions carefully because of possible complications related to treatment. There is also a need for further studies to determine whether treatment of patients who underwent liver transplant with TTR knock down therapy is efficacious in slowing progression of disease.