What is Amyloidosis? Why is timely and correct diagnosis is important? 1
Professor Sir Mark Pepys is a world leader in amyloidosis research and drug development. He discusses his lifetime’s work on amyloidosis diagnosis and treatment discovery. Professor Mark Pepys, you are a world leader in amyloidosis research and treatment. Dr. Anton Titov, MD. What is amyloidosis? Amyloidosis is a disease caused by the deposition of abnormal insoluble protein fibers. They are deposited in the extracellular space in various tissues and organs. There are many different forms of amyloidosis. Professor Dr. Mark Pepys, MD. Amyloidosis is characterized by different proteins. They form these fibrils. Protein type that makes the fibrils, eventually does not matter. The fibrils eventually look very similar histologically, morphologically, and by various imaging techniques. Fibrils have similar effects. They distort the structure and, therefore, the function of whatever tissue is involved. Amyloidosis is a rare disease. It is probably responsible for the deaths of about one in a thousand people in developed countries. So it is rare but not vanishingly rare. Professor Dr. Mark Pepys, MD. Amyloidosis is clinically very important. Because untreated amyloidosis is always fatal. Even with the best treatment currently available, amyloidosis is still fatal in nearly everybody who is ill with amyloidosis. Although survival is now much better than it was in the past. Dr. Anton Titov, MD. A major problem in the clinical recognition of amyloidosis and in its diagnosis is this. Amyloidosis is sufficiently rare that many doctors haven’t seen probably any cases. Perhaps doctors saw maybe only a few cases of amyloidosis in their whole clinical career. Professor Dr. Mark Pepys, MD. The other problem is that amyloidosis can present in almost any symptom at all. This is because systemic amyloidosis can affect any tissue throughout the body. The exception is the brain substance itself. Amyloidosis can present clinically with manifestations in any tissue or any organ. Therefore people don’t think of amyloidosis. Patients with amyloidosis can present with heart failure, or kidney failure. Patients with amyloidosis can have problems with their nerves, or their skin, or their liver, or their spleen. Professor Dr. Mark Pepys, MD. Any part of the body can be involved in amyloidosis. Any organ can be the main part that is involved in amyloidosis. Clinicians who are unfamiliar with the amyloidosis, don’t think of it. Therefore physicians don’t perform the correct diagnostic tests. They cannot diagnose amyloidosis. Doctors often don’t recognize it. Sadly, it is a very common experience that we have. Patients are diagnosed with amyloidosis relatively late in the course of disease. Dr. Anton Titov, MD. Correct diagnosis of amyloidosis is made often after several years of being ill. Patient is investigated by doctors sometimes in many different hospitals. Only then before somebody thinks of amyloidosis. Or the diagnosis is made by accident. Sadly that means that by the time patients come to us, it might be too late. We are experts in recognizing and treating amyloidosis. Even now, it happens. About a quarter of the patients have the commonest form of systemic amyloidosis. This is called AL amyloidosis. Patients still die within the first six months after being diagnosed. It is regardless of all the advances in treatment of amyloidosis. Amyloidosis is still a very major and serious unmet medical need. Professor Dr. Mark Pepys, MD. This is a reason why there is just 6 months survival after diagnosis of amyloidosis. It is the time lag before the correct diagnosis and initiation of therapy of amyloidosis. Patients go around and around to various doctors. Patients live for such a short time after the diagnosis is made. It is because patients already have irreversible damage to the organs. Dr. Anton Titov, MD. Amyloidosis particularly damages the heart. Amyloidosis also sometimes damages the kidneys and other organs. It may be difficult or impossible to salvage those failed organs. That is a major problem. The other problem in dealing with this relatively rare disease is this. Amyloidosis is so diverse. It is so complicated. The treatment requires really expert specialized clinicians. experts must have seen a lot of amyloidosis. Experts manage the problems all the time. This is a reason why the UK National Health Service funded us in 1999 as the National Amyloidosis Centre for the whole UK. We are funded directly by the Department of Health in the UK. Professor Dr. Mark Pepys, MD. We provide diagnostic and treatment advisory services for the whole national caseload of amyloidosis. That means we have a concentration of expertise here. This is certainly unique in this country. We are world-leading in amyloidosis. We see more patients and a greater variety of different types of amyloidosis than most other medical centers around the world. We have over 60 people in the National Amyloidosis Centre. We have senior and less senior clinicians, nurses, radiographers, scientists in the laboratory, administrative people. Professor Dr. Mark Pepys, MD. We see over 4,000 patients per year with amyloidosis. About 1,000 patients are new cases of amyloidosis. Other patients are follow-ups. This center was based on my invention in the 1980s. I invented a new technique for diagnosing and monitoring systemic amyloidosis. Dr. Anton Titov, MD. Until then the only method to diagnose amyloidosis was to have a tissue biopsy. You had to look at it under the microscope with appropriate special stains. That still is the gold standard for diagnosis of amyloidosis. But unfortunately these biopsies are very tiny. Professor Dr. Mark Pepys, MD. You can take a biopsy from the liver or the heart. But you have got an infinitesimally small sample of the whole organ. You cannot tell from that how much amyloid there is. You see amyloid only in your tiny biopsy. You don’t know where amyloidosis is in that organ or in other organs in the body. The only method of looking at the entire organ is this. You must assess the function of the affected organs. I developed a diagnostic technique for amyloidosis. A radioactive tracer is given to the patient. This tracer specifically localizes to amyloid deposits. It doesn’t go anywhere else. You can then image the patients after administering this tracer into a vein. Professor Dr. Mark Pepys, MD. You can see where the amyloid is located. You can identify whether amyloid is getting more or less. It is a quantitative diagnostic test. It is a very safe monitoring procedure. It is very informative about how much amyloid is present. We will know what is distribution of amyloid throughout the body. In its present form this diagnostic technique doesn’t show up amyloid in the heart. This is for various technical reasons. Dr. Anton Titov, MD. These problems are not possible to overcome. But fortunately we now have cardiac magnetic resonance imaging. This is an immensely powerful technique. Cardiac MRI enables a physician to diagnose, monitor, quantify and study in great detail and depth amyloidosis in the heart. MRI of the heart has been a very major recent advance. It was the development of that original tracer technique in the 1980s. Now we developed our clinical specialization. We were referred many patients. Because we were able to do more treatments for patients with amyloidosis. We helped patients more than other places. Professor Dr. Mark Pepys, MD. We are now funded by the UK Medical Research Council as a purely research endeavor. Then we became the de facto national referral center for amyloidosis over many years. Then in 1998-19999 the government set up this new scheme for specialist medical centers. They were dealing with relatively rare diseases. They wanted to focus on amyloidosis in just one or a few medical centers. We became the one National Amyloidosis Center.
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