Systemic Amyloidosis Treatment: Principles, Challenges, and New Therapies

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• Amyloidosis Treatment Principles
• Heroic Interventions to Sustain Patients
• Challenges in Amyloidosis Management
• Promising New Amyloid Removal Therapy
• Understanding Medication Development Process
• Full Transcript

Amyloidosis Treatment Principles

The fundamental goal of systemic amyloidosis treatment is to eliminate the precursor protein that forms amyloid fibrils. As explained by Dr. Mark Pepys, MD, this approach is the basis for all current therapeutic strategies. The treatment focuses on stopping the production of the abnormal protein, whether it originates from a monoclonal gammopathy or is a normal protein produced in excessive amounts.

Successfully removing the amyloidogenic protein halts disease progression and can lead to clinical improvement. Dr. Anton Titov, MD, and Dr. Mark Pepys, MD, emphasize that this strategy is central to patient survival. All other supportive care measures are designed to keep patients alive long enough for this primary treatment to take effect.

Heroic Interventions to Sustain Patients

Clinicians often employ aggressive measures to support patients with advanced amyloidosis. Dr. Mark Pepys, MD, describes going to extreme lengths, including organ transplantation. Kidney dialysis, kidney transplantation, liver transplantation, and heart transplantation are all utilized in comprehensive care.

These heroic interventions serve a critical purpose: they maintain organ function while treatments target the underlying protein problem. The objective is to provide a sufficient window of time for therapies to work on the fundamental disease process, ultimately aiming for long-term survival.

Challenges in Amyloidosis Management

Several significant challenges complicate amyloidosis treatment. A major issue is delayed diagnosis, as Dr. Anton Titov, MD, notes. By the time amyloidosis is identified, the disease is often too advanced for aggressive interventions to be viable.

Treatment resistance presents another hurdle. While modern therapies for monoclonal gammopathy are effective, they do not work for all patients. Furthermore, hereditary amyloidosis caused by gene mutations remains particularly difficult to treat, as current interventions cannot correct the underlying genetic error that produces the abnormal protein.

Promising New Amyloid Removal Therapy

A groundbreaking new treatment candidate offers hope for directly targeting amyloid deposits. Dr. Mark Pepys, MD, reports unprecedentedly encouraging results from this experimental therapy. For the first time, an intervention has been shown to actively remove existing amyloid from tissues in a short time frame safely.

This removal of amyloid deposits leads to measurable improvements in organ function, particularly in the liver. Dr. Pepys believes the major problem in amyloidosis is the physical disruption of tissue structure by amyloid deposits. By clearing these deposits, the new therapy directly addresses this core pathology, potentially benefiting patients for whom conventional protein-reduction strategies have failed.

Understanding Medication Development Process

It is crucial to understand the tenuous nature of drug development. Dr. Mark Pepys, MD, clarifies that most potential medications fail during development. The journey from laboratory invention to a licensed medicine involves extensive screening, animal studies, and clinical trials.

Dr. Anton Titov, MD, and Dr. Mark Pepys, MD, emphasize that until regulatory approval is granted, any treatment remains a "candidate" rather than a confirmed medicine. This new amyloid-removing therapy, while highly promising, is still in development. It is not a miraculous cure but represents a potential addition to the comprehensive approach needed to treat this complex disease effectively.

Full Transcript

Dr. Mark Pepys, MD: We have good treatment now for monoclonal gammopathy. It is the main cause of the commonest type of systemic amyloidosis. We hope that the new treatment would get rid of existing amyloid deposits and will have a big impact and enable people to stay alive long enough to benefit from interventions.

The basis of all our treatment of systemic amyloidosis is this: we try and get rid of the protein that is forming the amyloid fibrils. We work on a cure for amyloidosis.

Sometimes you can get rid of the abnormal protein. Sometimes it is a normal protein but you've got too much of it. Whatever it is, sometimes you can get rid of the precursor protein that makes the amyloid deposits. That is the method to stop the amyloidosis progressing and to make people feel better.

All current treatment consists of keeping the patient alive long enough to get rid of this precursor protein. We go to extreme lengths to treat amyloidosis: kidney dialysis, kidney transplantation, liver transplantation, heart transplantation. We pursue every possible measure to keep the patients alive long enough to get rid of the amyloid protein that is causing the damage in amyloidosis.

Unfortunately, you can't always do that. The patients with amyloidosis have a delayed diagnosis. Amyloidosis is so far advanced that you can't do these heroic measures, so you can't save them. Also, another problem is this: you can't always get rid of the abnormal protein.

We have very good treatment now for monoclonal gammopathy. This is the main cause of the commonest type of systemic amyloidosis. Sometimes those new amyloidosis treatments work; sometimes they do not work.

Then we have a group of hereditary amyloidosis diseases. There is a gene mutation that encodes an abnormal protein that makes amyloid. In such cases, we don't have any intervention that treats amyloidosis. These are very challenging amyloidosis cases to manage.

We hope that the new amyloidosis treatment would get rid of existing amyloid deposits. It will have a big impact and enable people to stay alive long enough to benefit from amyloidosis therapy. This therapy could work for the people with genetic amyloidosis disease. They would need to have obviously repeat dosing of our treatment. Patients can keep getting rid of the amyloid; amyloidosis will otherwise recur.

Our proposed treatment is not a miraculous amyloidosis cure. It requires the other interventions. You always have to be doing the other things to treat amyloidosis. It is important to understand that.

Dr. Anton Titov, MD: The other thing that is very important to understand is this: the very tenuous nature of medication development. Most medication development fails. Very few amyloidosis medications start off with an invention in the laboratory. There is a screening of amyloidosis compounds. The animal pharmacology and toxicology is done. Eventually, amyloidosis treatment candidate gets into patients. Most of them don't benefit from amyloidosis treatment. They fail for a wide variety of reasons.

It is not the subject of this interview, but this is a well-recognized phenomenon. Until the medication is actually licensed by the regulatory authorities, we can't really say "it is a medication" or "it is a medicine". It is not. It is a “candidate". It is something that we are trying to develop for amyloidosis. It is exactly the same with this amyloidosis treatment.

Dr. Mark Pepys, MD: We are optimistic about it. We are hopeful. The results of amyloidosis therapy so far are unprecedentedly encouraging. We have actually shown for the first time there is an intervention that can make amyloid go away. It removes amyloid in a short space of time. It can remove amyloid safely. Furthermore, it shows that it benefits the patients with amyloidosis.

Dr. Anton Titov, MD: People are still arguing how exactly amyloid causes amyloidosis. My belief has always been that the major problem caused by amyloid deposits is the disruption of the structure and function of the tissues. The evidence is in favor of this amyloidosis theory.

We've got a treatment that makes amyloid disappear. What happens? Organ function gets better in the liver. It is easy to measure organ function. That is what we have done so far. Sometimes we can do the same thing in the heart. It will be wonderful.

Dr. Mark Pepys, MD: We haven't got there yet. But at the moment, this is a candidate amyloidosis treatment. It is not a medicine yet. We need to be straight about that.

Dr. Anton Titov, MD: How might your medication work for the Alzheimer's disease treatment?