Last Saturday I drove to the quarterly Northern California Amyloidosis support group held at the Walnut Creek Kaiser. It was wonderful to reconnect with so many friends and fellow patients. Charlesetta looks great after her bone marrow transplant. She's like me, first a heart then BMT. Dena had invited the chief science officer from Prothena to speak about their new drug in phase 1 clinical trials to target amyloidosis, NEOD001. THIS IS REALLY IMPORTANT. Never has a company targeted a drug to only treat amyloidosis. Most of our current drugs we borrow from the world of multiple myeloma. The main paradigm shift is that we can now focus, not just on the plasma cell, but rather the toxic light chain proteins themselves.
This is tricky. The light chain has two parts: The hypervariable region and the constant region. The hypervaiable region is like a snowflake; no two are alike. Concomitantly each patient's bad light chain is also different, likely arising from a random mutation in this same region. As such, no one drug (antibody) could target them all. Additionally, if you designed the drug to attack the constant region, it would attack all of our antibodies, both the good, the bad and the ugly. Alas, how do we correct this conundrum? Aha! The cleverness of y'all. First you ask, "What is common to all misfolded light chains? Answer: they are misfolded. When normal good-guy antibodies correctly fold they hide, or physically cover a region that is common to all light chains. Misfolded bad light chains swing open, like a gate on a hinge and, Viola! the cryptic epitope is now exposed and visible. NEOD001 is an antibody that is designed and produced in manufactured cell cultures. It specifically targets this previously hidden amino-acid sequence, activates the immune response and the terminator arrives to clean up the mess. The toxic villains are neutralized and removed from both the serum and the tissues. The normal, good-guy antibodies are unaffected because this target sequence is still hidden deep inside; unavailable to the drug. Wow, what a concept.
One of our group members in currently in the study and shared that he seems to be doing just fine with no untoward effects. We thanked him for doing this for us.
One of our group members in currently in the study and shared that he seems to be doing just fine with no untoward effects. We thanked him for doing this for us.
This changes everything, if it works.
Until now, I have always considered amyloidosis incurable. My current fight is not to be cured, but rather to shut down my plasma cells with drugs so that fewer light chains are floating around to attack my new heart.
Now, by detoxifying the rogue light chains, it isn't exactly the definition of cure, but it feels the same. It is possible that we will stop using the term fatal with this disease. We will manage our disease and move on with our lives.
That would be nice
Kevin
P.S. I like that the Prothena logo looks like a gamma-globulin (antibody) designed to look like a "P"
