Professor Sinéad M Murphy
Consultant Neurologist, Tallaght University Hospital, Clinical Associate Professor, Trinity College Dublin,
Clinical Lead Irish site for European Reference Network- Rare Neurological Disorders (ERN-RND)
Transthyretin (TTR) amyloidosis presents with a wide range of symptoms, meaning that patients often consult multiple specialists. Unfortunately, delays in diagnosis remain a challenge.
Many TTR amyloidosis patients experience symptoms for years before receiving a diagnosis, by which time their condition is often advanced and harder to treat. To address this, a group of clinicians formed a Working Group to develop an Amyloidosis Model of Care, which was approved in 2022. The goal is to reduce diagnostic delays, expedite access to treatment and improve patient outcomes.
Presenting TTR amyloidosis symptoms
- Neurological: Peripheral neuropathy (numbness, tingling, pain, weakness)
- Autonomic neuropathy (orthostatic hypotension, diarrhoea, erectile dysfunction, impaired bladder and bowel control)
- Carpal tunnel syndrome
- Spinal stenosis
- Cardiac: Cardiomyopathy (heart failure, arrhythmias)
- Gastrointestinal: Nausea, diarrhoea, constipation, weight loss
- Musculoskeletal: Joint pain, biceps tendon rupture
Advancements in treatment
Until October 2021, Ireland had no disease-modifying treatments for TTR amyloidosis. Management was symptomatic, aiming to relieve symptoms as best as possible. Patients experienced a gradual and relentless decline, typically succumbing to the disease 5–10 years after symptom onset due to heart failure, autonomic dysfunction and weight loss.
Thankfully, major treatment advances have changed the outlook for patients. Several medications now alter the natural history of the disease, such as tafamidis and genetic therapies including patisiran, vutrisiran and inotersen.
These therapies have been life-changing for many patients. While the primary aim of treatment is to stabilise the condition and slow progression, some patients experience improvements, particularly in autonomic or sensory symptoms. Early treatment initiation leads to better outcomes.
These therapies have been
life-changing for many patients.
Multidisciplinary care approach
Managing TTR amyloidosis effectively requires close collaboration between cardiologists and neurologists to tailor treatment plans. At Tallaght University Hospital’s Neuropathy Clinic and the Mater University Hospital’s Cardiac Amyloidosis Clinic, working as part of the Model of Care proposed Irish Expert Amyloidosis Network, Professor Joyce and I conduct regular multidisciplinary amyloidosis meetings. These sessions enable us to discuss cases and determine the most appropriate treatment strategy for each patient.
Future directions and ongoing research
TTR amyloidosis research is evolving rapidly. An upcoming trial aims to investigate whether treating pre-symptomatic TTR mutation carriers can delay disease onset. Additionally, exciting new therapies are on the horizon, offering hope for even better treatment options.
The landscape of TTR amyloidosis treatment has shifted dramatically. Just a few years ago, we had few therapeutic options to offer patients. Today, the field is advancing at an unprecedented pace, bringing real hope to those affected.
