Amyloidosis is a group of diseases in which abnormal proteins known as amyloid fibrils build up in various tissues including the kidney, heart, liver, skin, and nervous system resulting in a variety of clinical sequelae including organ dysfunction and death. There are over 23 unrelated proteins known to form amyloid fibrils, many of which are aggregates of misfolded proteins that are neither biodegradable nor can be recycled by our bodies. 

Abnormal Immunoglobulin light chains known as AL (amyloid light chain), transport protein transthyretin (ATTR) which normally transports retinol and thyroxine, and amyloid A (AA) are some of the better recognised examples of amyloid proteins. 

It is important to note however that hereditary, dialysis associated, localised and ocular forms also exist, and Beta protein precursor is implicated in Alzheimer syndrome as are other amyloid fibrils in different dementia diagnoses.

The quoted incidence of amyloid disease is 12 per million and it is estimated that over 20 000 cases of amyloid are undiagnosed and untreated in Australia alone. It is noteworthy that 13-17% of patients with heart failure and degenerative aortic stenosis have amyloidosis and that up to 50 % of patients with amyloid see five doctors before a diagnosis is made. Up until recently only a four-year life expectancy was anticipated, fortunately pharmacological breakthroughs are expanding this horizon. 

Although the term amyloid was originally coined by German botanist Mathias Schleiden to describe the normal amylaceous of plants, it was Rudolf Virchow in 1854 who adopted the term to describe abnormal extracellular material seen in the liver during autopsy. 

As we will explore in this podcast we now think of amyloid disease in terms of primary systemic amyloid (AL) where a clone of abnormal plasma cells secretes excess immunoglobulin light chains that misfold and aggregate as non-biodegradable non-recyclable amyloid fibrils. Such a clone is also observed in about 5 % of myeloma diagnoses and about 12% of MGUS (monoclonal gammopathy of uncertain significance). 

Additionally, age associated amyloid transport transthyretin protein ATTR is an acute phase reactant produced predominantly in the liver in response to multiple cytokines which may become amyloid in form with senescence depositing in the heart and kidneys where diastolic dysfunction and renal impairment develop.

In this podcast I was curious to explore how we can improve our surveillance for this condition and to raise our awareness. I was also keen to understand how to confirm the diagnosis and to explore treatment options.

To explore this interesting area further please welcome to the podcast Dr Simon Gibbs from Precision Haematology who is a clinical haematologist and amyloidosis specialist, and a Senior adjunct lecturer at Monash University.

After attaining his medical degrees from the University of Melbourne he moved to Cambridge in the United Kingdom to gain further experience in autologous and allogeneic bone marrow transplantation as treatment for myeloma and leukaemia and completed a four-year fellowship at the National Amyloidosis Centre at University College London, focusing on novel therapies for AL amyloidosis. 

Upon returning to Australia, he was appointed the Myeloma Lead at Eastern Health and established the Victorian and Tasmanian Amyloidosis Service (VTAS). 

He is the Chair of the Australian Amyloidosis Network (www.amyloidosis.net.au), and a member of the Haematology Society of Australian and New Zealand (HSANZ). He serves on both the Educational Subcommittee for the International Society of Amyloidosis, and the Medical and Scientific Advisory Committee (MSAG) for Myeloma Australia and is the author of over 40 publications in international medical literature. 

References :

Dr Simon Gibbs: https://precisionhaematology.com.au/doctor/dr-simon-gibbs/

Australian Amyloidosis Network: https://aan.org.au/