Anti-MAG peripheral neuropathy (Immunoglobulin M(IgM) Anti-Myelin Associated Glycoprotein Peripheral Neuropathy) is a rare autoimmune variety of peripheral neuropathy. In this type of PN, a person’s own immune system attacks cells that are specific in maintaining a healthy peripheral nervous system. As these cells are destroyed by antibodies, they lose function and create problems in both sensory and motor function.
This form of neuropathy is extremely difficult to diagnose and treat; but with more research being conducted, more answers are becoming known.
Q&A with Dr. Richard Lewis, MD
On June 27, 2022, the Foundation for Peripheral Neuropathy (FPN) welcomed Richard Lewis, MD, from Cedars-Sinai Medical Center, to present on Anti-MAG peripheral neuropathy. During this 60-minute recorded program, Dr. Lewis provided a scientific overview of anti-MAG PN, from diagnosis to treatment and everything in between. Following the session, Lindsay Colbert, Executive Director of FPN, sat down with Dr. Lewis to ask some questions that were not addressed during the program:
Q: Dr. Lewis, you mentioned a drug during the webinar that was being tested and said it proved to be toxic. Can you please remind us of the drug you were referencing?
A: The toxic drug being tested was the glycoprotein created by Polyneuron Pharmaceuticals.
Q: Is a diminished energy level a result of Anti-MAG PN?
A: Yes and no. A lack of energy is a non-specific symptom of anti-MAG. Diminished energy is very common in many neuropathies.
Q: Can someone with MGUS (monoclonal gammopathy of undetermined significance) donate blood?
A: That is a great question, and I am not 100% certain. I’d encourage any patient who has MGUS to reach out to the blood donation center to see if there are any limitations for blood donations.
Q: How do you check if Anti-MAG is progressing in a patient? Do you recommend an EMG or any specific blood tests, for example?
A: Clinical progression of symptoms is the most important data point to monitor. An EMG is not usually used to monitor disease. In terms of bloodwork, IgM levels is most important, and Anti-MAG titers may help too. (Note: A titer is a laboratory test that measures the presence and amount of antibodies in blood. A titer may be used to prove immunity to disease. A blood sample is taken and tested.)
Q: Is Anti-MAG neuropathy in any way related to HIV-related neuropathy?
A: Anti-MAG PN and HIV-PN are both a type of neuropathy, but they have different causes.
Q: Why with exercise do anti-MAG patients often become even weaker and sometimes down for days?
A: That is a great question. I am not certain why a patient who is affected by neuropathy becomes weaker after exercise. Everyone responds differently. That being said, it’s important to know that exercise does not make this disease worse. Sometimes, however, exercise can cause fatigue if you are weak, and you try to do more than your nerves and muscles can handle. Please work with your doctor on developing and maintaining a proper exercise routine, as exercise is important for overall health.
Q: Is tremor common with IgM anti-MAG PN?
A: Yes, tremor is a common symptom of this disease.
Q: Do all neuropathy causing antibodies have a monoclonal spike or is that specific to Anti-MAG only?
A: Many neuropathies with defined antibodies have IgM spike; but some, like anti-neurofascin and contactin have IgG4 and may not have paraprotein. Some anti-MAG may not have identified MGUS.
Q: Is rituximab + bendamustine treatment same as Rituximab + B cell Depletion?
A: Bendamustine is not a B cell depleter, but is an alkylating agent used in lymphomas. The combination is stronger but has more risk than rituximab alone (which is a B cell depleter).
Q: Can Anti-MAG affect the brain in patients too?
A: No, I am not aware of Anti-MAG ever affecting the brain. Unfortunately, I couldn’t find much in the literature of brain involvement with this condition either.
Q: What is a normal serum level of IgM?
A: Serum levels can vary by lab, but usually < 200 is considered “normal.”
Q: Is ibrutinib effective treatment for anti-Mag?
A: A small series of studies suggest efficacy with using Ibrutinib as a treatment for this condition. Anything that treats B cell lymphomas or IgM related malignancies may help anti-MAG, but risks always need to be considered. Before you undergo a new treatment regiment, please consult with your primary care physician or neurologist to ensure that this is safe and appropriate for you personally.
Q: What causes or starts anti-Mag?
A: Anti-MAG starts with the paraprotein and may not manifest neuropathy symptoms for years.
Q: Would one expect that progression of the demyelination is unlikely to be the same in both legs?
A: This disease ispretty symmetric. I would expect both legs to show some nerve conduction changes, although not necessarily the exact same.
Q: During this program, you mentioned a certain vitamin supplement that should be avoided by people with Anti Mag PN. Can you please remind us of what that vitamin supplement was?
A: Yes, of course. It was vitamin B6, because taken in excessive amounts, B6 may cause painful neuropathy. Please check your own vitamin levels first to confirm your levels are depleted before taking any supplement.
Q: Can the Antibody from Mag travel and attack another part of the body’s organs?
A: No, I am not aware of anti-MAG antibodies affecting other organs.
Q: What are your thoughts about Brukinsa as it appears to be bringing down a patient’s IgM levels?
A: Brukinsa is another class of medications (kinase inhibitor) used to treat lymphomas. I would expect it to reduce IgM levels and help anti-MAG neuropathy. Rituximab and appropriate chemotherapy appear to be more effective than rituximab alone but have more risks.
Q: Can you please highlight any research opportunities available today for patients with anti-MAG to participate in?
A: Yes, as the Foundation knows, the iMAGiNe Study is currently enrolling anti-MAG patients at various sites in Europe and the U.S.A.
Dr. Lewis, thank you so very much for your time and expertise. FPN is extremely grateful for the support you are helping to provide to patients affected by anti-MAG peripheral neuropathy.