MGA News July 1997

Introduction and Clinical Background

About one in ten Myasthenia Gravis (MG) patients has a thymoma; if so, they are usually over 30 when diagnosed, and show no major male/female bias.

Like most tumours, thymomas can cause trouble if not treated in good time. But the good news is that they are seldom highly malignant, and usually behave more like a rodent ulcer, spreading locally rather than by the blood stream. Most of them can be removed completely. Even if not, they can then usually be held in check for many years by radiotherapy or chemotherapy, if necessary.

The myasthenia in thymoma patients involves many of the body muscles and not just those that move the eyes. It responds similarly to the same drug treatments as in most other MG patients, because it is caused by a similar immune attack on the muscles, in particular on their 'ignition system' - the acetylcholine receptor (AChR). Thymectomy is a vital part of the treatment plan because the extra disabilities in thymoma patients are mostly caused by the tumour, which should always be removed as soon as patients are fit enough. Disappointingly, their myasthenia does not usually improve as much as in young myasthenics without a thymoma.

While the myasthenia may be disabling, it does act as a valuable warning sign; it often leads to earlier diagnosis of the thymoma which otherwise can easily grow unnoticed. We estimate that about a third to a half of all thymoma patients develop MG (in a few, the MG even starts after thymectomy! Very interestingly, about one in twenty have other autoimmune disorders, sometimes affecting the bone marrow and causing anaemia.

The hunt for the cause: lessons from the LEMS

For us researchers, the special links between autoimmunity and particular kinds of tumours hold precious clues about how the immune attack on our own tissues might get started. The LEMS is a particularly telling example. About half of the patients have 'small cell' lung tumours. Dr Bethan Lang (in our team) has shown that some common factor in these tumours immunises the patients. Just as when we are immunised against 'flu or tetanus, they then start to make antibodies, and some of these attack a related factor in the nerve endings and cause muscle weakness. Beth's team is busily trying to pin down the exact factor and why it immunises so well. Also, as in MG, we would love to know why a similar process can also happen in the permanent absence of any such tumour.

New findings in MG Thymomas

We believe that the same kind of process happens in MG thymomas as in the LEMS, though the picture is more confusing.

To search for the triggering spark, Nita Negvekar (in our team) is growing the 'scaffolding' cells from thymomas, and Dr David Beeson and colleagues are identifying which muscle proteins they may produce. They have recently found one particular part of the AChR, and Nita is now testing whether the thymic white blood cells (T cells) in the thymomas are reacting against it. Because these T cells control antibody responses, Nita has been cloning them from thymomas for some years. With one earlier clone, she is hoping soon to test a new 'magic bullet' treatment designed specifically to turn off these T cells without suppressing the whole immune system.

This approach has already given very promising results with another clone, but we were worried that it would have to be tailor-made for each patient. However, Dr Marguerite Hill is now finding that similar clones from young myasthenics all tend to recognise exactly the same part of the AChR; if this proves to be a general rule, we hope to be able to produce a more widely applicable magic bullet. All of this proves to us that our work is not just an academic exercise, and we remain as grateful as ever for your loyal support in helping us to keep it on the boil.

MGA NEWS July 1997

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