Impact of High-Dose Tafamidis on Hereditary ATTR (ATTRv) Amyloidosis With Central Nervous System Involvement: Two...

Treatment options for central nervous system (CNS) manifestations of ATTRv amyloidosis remain limited, with no disease-modifying therapy. However, previous case series have indicated that tafamidis (a transthyretin stabiliser) crosses the blood-brain barrier in small quantities. We present long-term follow-up data on two patients with CNS manifestations of ATTRv who received high-dose (61 mg) oral tafamidis.

Patient one is a 48-year-old man with p.Gly73Ala ATTRv peripheral neuropathy and commenced on gene-silencing therapy. He was subsequently diagnosed with early ATTRv CNS involvement, prompting the addition of tafamidis since age 45. Patient two is a 27-year-old woman with p.Gly67Arg ATTRv with significant CNS involvement resulting in epilepsy and encephalopathy. Since age 21, she has been on gene-silencing therapy and tafamidis.

Following 3 years of therapy, patient one has remained clinically asymptomatic. However, brain magnetic resonance imaging (MRI) and cerebrospinal fluid assessment have demonstrated progression of his CNS ATTRv. Followed 6 years of therapy, patient two has continued to have seizures requiring escalation of anti-seizure medications and MRI brain has shown progression of CNS disease.

In our two patients, progression of CNS disease occurred whilst on high-dose tafamidis, highlighting the importance of further studies into the monitoring and treatment of CNS manifestations of ATTRv.