Understanding Amyloidosis: Causes, Diagnosis Challenges, and Treatment Research

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• Amyloidosis Diagnosis Challenges
• Link to Multiple Myeloma
• Amyloid Formation Process
• Body Clearance Mystery
• Treatment Research Directions
• Full Transcript

Amyloidosis Diagnosis Challenges

Diagnosing amyloidosis presents significant clinical difficulties according to Dr. Mark Pepys, MD. The disease manifestations are extremely varied and can mimic many other common conditions. This variability means physicians often do not consider amyloidosis in their initial differential diagnosis.

Dr. Anton Titov, MD, discusses with Dr. Pepys how this diagnostic oversight leads to delays in ordering the correct tests. The definitive diagnostic test for amyloidosis is a tissue biopsy examined under a microscope. Dr. Mark Pepys, MD, emphasizes that suspected cases should be referred to specialized centers for advanced imaging and diagnostic procedures.

Link to Multiple Myeloma

Amyloidosis has important connections to plasma cell disorders like multiple myeloma. Dr. Mark Pepys, MD, explains that multiple myeloma represents a malignant cancerous disease within the monoclonal gammopathy spectrum. The same plasma cells that become cancerous in myeloma can also cause amyloidosis without being malignant themselves.

Dr. Anton Titov, MD, and Dr. Pepys note that these non-cancerous cells don't replicate uncontrollably or invade organs. Instead, they produce abnormal proteins that form amyloid deposits. The most common type of systemic amyloidosis is caused by these plasma cell-derived proteins, creating diagnostic confusion between the two conditions.

Amyloid Formation Process

The fundamental process in amyloidosis involves protein misfolding and aggregation. Dr. Mark Pepys, MD, uses the analogy of egg white transformation to explain this concept. Normally soluble proteins become insoluble through physical state changes, similar to how liquid egg white turns solid and opaque when cooked.

Approximately 30 different proteins in the human body can misfold and form amyloid fibrils. These proteins undergo structural changes that cause them to aggregate into clumps. The insoluble fibrils then deposit in tissues throughout the body, disrupting normal organ function.

Body Clearance Mystery

A major unsolved mystery in amyloidosis involves the body's failure to clear abnormal protein deposits. Dr. Mark Pepys, MD, explains that the human body typically excels at removing abnormal debris through specialized cells called macrophages. These cells efficiently clear blood clots, broken bone fragments, and other damaged tissue without medical intervention.

Dr. Anton Titov, MD, discusses with Dr. Pepys why this clearance mechanism fails with amyloid deposits. The mystery deepens because amyloid consists of the body's own proteins in abnormal physical form rather than foreign material. This failure of macrophage recognition and clearance represents a fundamental gap in understanding amyloidosis pathophysiology.

Treatment Research Directions

Dr. Mark Pepys, MD, has focused his research career on understanding and addressing the clearance failure in amyloidosis. His work investigates why macrophages cannot recognize and remove amyloid deposits despite their efficiency with other types of cellular debris. This research has direct therapeutic implications for developing effective amyloidosis treatments.

Dr. Pepys tells Dr. Anton Titov, MD, that researchers are making significant progress toward successful therapeutic interventions. By targeting the clearance mechanism failure, new treatments aim to help the body naturally remove existing amyloid deposits. This approach represents a promising direction beyond simply reducing new amyloid production.

Full Transcript

Dr. Anton Titov, MD: Amyloidosis causes are explained by the world’s leading amyloidosis diagnosis and treatment expert. How is amyloidosis related to multiple myeloma, a form of leukemia?

The problem with the diagnosis of amyloidosis is that the manifestations are so varied. Amyloidosis symptoms can mimic many other diseases. A doctor may not think of amyloidosis. A physician may not do the correct diagnostic test.

Dr. Mark Pepys, MD: The correct diagnostic test in amyloidosis is a biopsy. Then a physician looks at it under the microscope. It is best to refer the patient to us. We can do our imaging diagnostic procedures.

Dr. Anton Titov, MD: It is very difficult to make the diagnosis of amyloidosis. The main problem is to think of the correct diagnosis.

You mentioned a celebrity individual. His diagnosis of multiple myeloma might not have been very far from the correct diagnosis. Because multiple myeloma is part of a group of diseases called monoclonal gammopathy. Multiple myeloma is a malignant cancerous disease.

But the same cells that are cancerous in myeloma can also cause amyloidosis.

Dr. Mark Pepys, MD: Multiple myeloma itself can cause amyloidosis. Similar cells or the same cells can cause amyloidosis. In fact, the commonest type of systemic amyloidosis is caused by these cells.

The cells themselves are not cancerous. They don't replicate out of control. They don't invade anywhere else.

Dr. Anton Titov, MD: These cells don't damage the local organs where they are. Cells just produce an abnormal protein. It forms the amyloid deposits.

Dr. Mark Pepys, MD: The key thing that is happening in amyloidosis is the formation of amyloid. You have normally soluble proteins. For example, egg white. It is true and translucent when the protein is soluble. Then you fry your egg or boil it. Egg white becomes insoluble, hard and white, and opaque.

Dr. Anton Titov, MD: So proteins can be in different physical states. There are about 30 different proteins in the body that are normally soluble. They can misfold and become abnormal. Insoluble proteins deposit as amyloid fibrils.

There are aggregates, clumps of these proteins. They have undergone a change in their physical form. They become insoluble. They lay themselves down in the tissues of the body.

The mystery is not why this happens. Because now we understand that in recent years rather well. We understand the physical and biophysical processes of amyloid fibril formation.

The big mystery is why doesn't the body get rid of abnormal proteins? Normally the body is extremely efficient at getting rid of abnormal debris.

Sometimes you break your leg. You perhaps fell off your bicycle. You have a pint or two of blood in your leg and broken bones. As long as you don't get infected, the body heals it all up very well. Everything gets remodeled and returned to its normal anatomy.

Blood clots get removed. The bruising goes away. If you have a bruise, nothing terrible happens. It all clinically silently fades away.

Because there are special cells in the body. They are called macrophages. Macrophages are very competent at recognizing abnormal debris. They clear debris away.

The mystery is this: why do they not remove amyloid deposits? These are debris that are made of the body's own proteins. Debris are not made of anything abnormal from the outside. It is just the normal proteins in an abnormal form.

That is a big mystery.

Dr. Mark Pepys, MD: Nobody has solved this mystery. But that has been my key interest in treating amyloidosis now for many, many years.

I am trying to understand why that failure of clearance exists. I am trying to remedy it with therapeutic interventions. We are now reasonably well on the way to treat amyloidosis successfully.