|
Welcome to Butterfly News October, the newsletter from The Lupus
Site - www.uklupus.co.uk
Apologies for there being no September issue. Shar
has had computer and health problems, and I haven't been too good,
along with trying to run my business and buying a house!
Today sees the start of Lupus Awareness Month in the
US, and also for the first time in the UK. Lets hope that together
we can raise public awareness of this disease. Lupus UK - http://www.lupusuk.com
Lupus Foundation of America - http://www.lupus.org
News of a new test that could be used to help diagnose
lupus can be found in the news section at - http://www.uklupus.co.uk/lupusnews.html
Butterfly News archive - http://www.uklupus.co.uk/bnews.html
THE STATE OF LUPUS RESEARCH
INTRODUCTION
Lupus erythematosus-whether systemic,involving any
part of the body (SLE), or discoid (cutaneous), involving only the
skin (DLE)-is a chronic inflammatory disease that can affect variousparts
of the body, especially the skin, joints, blood,and kidneys.
Currently there are few drug therapiesspecifically
approved for lupus by the Food and Drug Administration (FDA). All
of the following therapies are investigational and are in various
stages of research and/or clinical trials.
HOW LUPUS AFFECTS THE BODY
The body's immune system normally makes proteins
called "antibodies" to protect the body against foreign materials,
or "antigens," such as viruses and bacteria. In an autoimmune disorder
such as lupus, the immune system loses the ability to tell the difference
between its own cells and tissues and the unwelcome antigens. The
immune system then makes antibodies directed against "self." These
"autoantibodies" react with the self antigens to form "immune complexes,"
which build up in tissues and can cause inflammation, injury to
tissues, and pain.
The course of lupus appears to depend heavily upon
the activity of autoimmune "lymphocytes," including B cells that
produce autoantibodies, and T Cells which regulate the B cells in
the development of the immune response.
Current therapies for lupus try to suppress the entire
immune system and to reduce inflammation. The aim of the future
is to determine the specific mechanisms of inflammation and autoimmunity,
in order to better target therapies to what is going wrong, without
suppressing the whole immune system. Medical research is ongoing
on the treatments listed here.
BIOLOGIC AGENTS AND IMMUNE-SUPPRESSANTS
DHEA (PrestaraT)
It is thought that androgens (male hormones) may reduce
lupus disease activity. DHEA is a mild male hormone, which appears
in abnormally low levels in persons with lupus. Studies have shown
that DHEA was helpful in treating mild to moderate lupus, and may
be particularly useful for persons experiencing cognitive dysfunction
and fatigue. Study results also showed a significant increase in
bone density.
The FDA did not approve DHEA for use in lupus, on
the basis of studies that tested its ability to reduce disease activity.
However, the agency has approved ongoing studies to further test
the product's safety and effectiveness in protecting the bones.
LJP 394
Some persons with lupus produce antibodies to double-stranded
DNA (dsDNA). This response is believed to promote lupus kidney disease,
which is one of the more serious complications of lupus. The drug
candidate LJP 394 has been developed to lower the levels of these
antibodies and is currently being studied to see whether it can
reduce kidney flares.
Antibody to CD40 Ligand
Research in this area has focused on proteins located
on B cells and T cells that are important for the stimulation of
these cells. White blood cells help fight off foreign intruders,
but can be overactive in lupus. One way in which this happens is
that a T cell protein known as CD40L might over-stimulate a B cell
protein known as CD40. By blocking the communications between these
proteins, it may be possible to help correct the hyper-activity
of the immune system which is characteristic of lupus. Anti-CD40L
antibodies for SLE are proteins much like those our bodies produce,
but they are designed to target CD40L and block its increased activity
in lupus. The concept here is that autoantibodies are not necessarily
bad in the right dose and with the right target. Unfortunately,
these drugs are not being actively developed for lupus anymore,
because of a significant risk of blood clotting problems in previous
trials. It is not yet known whether these blood clotting problems
could be prevented and if these drugs could be safely used in patients.
BlyST
Several companies are now studying this new treatment
strategy for lupus. This antibody targets another B cell-regulating
protein which is found on a different white blood cell called a
monocyte. The product that is furthest along is an antibody to BlyS
(short for B Lymphocyte Stimulator) and seems to control how reactive
a B cell might be to a T cell. The purpose of this new medication
is to try and dampen that process.
LJP 1082
This product is under development for persons who
suffer from antibody-mediated thrombosis. Also known as the Antiphospholipid
Syndrome (APS), persons with lupus face an increased risk of blood
clots that can result in stroke, heart attacks, deep-vein thrombosis,
recurrent miscarriages, and blood clotting complications after surgery.
Antiphospholipid antibodies are common in persons with lupus and
are thought to contribute significantly to the increased risk for
blood clots.
Bromocriptine (Parlodel TM )
This molecule has been shown to suppress the secretion
of prolactin, and to suppress circulating prolactin. Prolactin,
or PRL, is believed to be involved in the onset and progression
of lupus. (Prolactin is best known as a hormone that promotes and
supports lactation in mammals.) In studies, prolactin was found
to be necessary to maintain normal immune function. Therefore, bromocriptine's
ability to suppress both prolactin and circulating prolactin might
lead to suppression of the immune system and autoimmune disease.
High Dose Intravenous Immunoglobulins
One way to regulate, rather than suppress, the body's
immune response is by manipulating the autoantibodies. Giving high
doses of immunoglobulins (a mixture of normal antibodies) intravenously,
known as IVIg or IVIG antibodies, has been used for lupus kidney
disease and other serious manifestations of lupus for ten years.
Mycophenolate mofetil (CellCept®)
Mycophenolate mofetil is approved to prevent rejection
after organ transplants. This is important to persons with lupus
since some people with serious kidney disease may require a transplant.
Physicians have now begun to use CellCept to control the activity
of various rheumatic diseases. Anecdotal reports suggest that it
might be effective in lupus kidney disease. There is an ongoing
FDA-sponsored trial to compare mycophenolate mofetil with Cytoxan
for this purpose.
Cyclosporine (Sandimmune®, Neoral®)
This potent immunosuppressive drug is frequently used
in the therapy of autoimmune diseases, including systemic lupus.
Small, uncontrolled studies have shown significant improvement in
disease activity and consistent reduction in corticosteroid dosage,
often by as much as 50 percent. Toxicity does occur, especially
in individuals with hypertension and kidney impairment, but usually
reverses as the dose is reduced or an antihypertensive agent is
added.
Thalidomide (Thalomid®)
Thalidomide, developed as a sleep aid in the 1950s,
has been increasingly accepted as a second-line therapy for the
types of lupus that affect the skin, producing marked improvement
even in patients who have not responded to numerous other treatments.
Rituximab (Rituxan®)
Anti-CD20, known as rituximab, or Rituxan, is a new
genetically- engineered monoclonal antibody that targets a receptor
called CD20, found on some B cells. The antibody marks the B cells
for destruction by the immune system, after which new B cells are
generated by stem cells. Stem-cells and B cells bearing antibodies
are spared by Rituxan, since they lack the CD20 antigen.
PROCESSES TO CLEANSE THE IMMUNE SYSTEM
Apheresis, or Plasmapheresis
This is a safe but expensive and labor-intensive procedure,
whereby plasma is separated from whole blood in order to remove
undesirable substances from the blood. Some of the reasons one might
undertake plasmapheresis for systemic lupus are to remove circulating
immune complexes and autoantibodies and to improve the functioning
of suppressor cells and the cells that kill bacteria. Anecdotal
reports have suggested that this treatment might be helpful for
individuals who are quite ill.
Hematopoietic Stem Cell Transplantation
In this procedure, stem cells harvested from the person
are "cleansed" and returned to repopulate the bone marrow. It is
thought that they might also contribute to organ repair over the
following years. The underlying concept is based on the theory that,
for most people, lupus is not simply an inherited disease. That
means that the body's primitive, immature, and undifferentiated
"stem" cells are not inherently "lupus" stem cells. The disease
develops because a person carries a genetic predisposition to lupus,
and certain factors in their environmental and hormonal make-up
compound that risk, allowing the disease to come forth. Therefore,
if a person's stem cells are allowed to develop in a safer environment,
a more normal immune response might emerge
>From The Lupus Foundation of America www.lupus.org
---------------------------------------------
Butterfly News Copyright 2002, The Lupus Site
http://www.uklupus.co.uk
|
Message
Boards
