Can MS be Treated?
There is as yet no cure for MS. Many patients do
well with no therapy at all, especially since many
medications have serious side effects and some carry
significant risks. Naturally occurring or
spontaneous remissions make it difficult to
determine therapeutic effects of experimental
treatments; however, the emerging evidence that MRIs
can chart the development of lesions is already
helping scientists evaluate new therapies.
In the past, the principal medications physicians
used to treat MS were steroids possessing anti-inflammatory
properties; these include adrenocorticotropic
hormone (better known as ACTH), prednisone,
prednisolone, methylprednisolone, betamethasone, and
dexamethasone. Studies suggest that intravenous
methylprednisolone may be superior to the more
traditional intravenous ACTH for patients
experiencing acute relapses; no strong evidence
exists to support the use of these drugs to treat
progressive forms of MS. Also, there is some
indication that steroids may be more appropriate for
people with movement, rather than sensory, symptoms.
While steroids do not affect the course of MS
over time, they can reduce the duration and severity
of attacks in some patients. The mechanism behind
this effect is not known; one study suggests the
medications work by restoring the effectiveness of
the blood/brain barrier. Because steroids can
produce numerous adverse side effects (acne, weight
gain, seizures, psychosis), they are not recommended
for long-term use.
One of the most promising MS research areas
involves naturally occurring antiviral proteins
known as interferons. Three forms of beta interferon
(Avonex, Betaseron, and Rebif) have now been
approved by the Food and Drug Administration for
treatment of relapsing-remitting MS. Beta interferon
has been shown to reduce the number of exacerbations
and may slow the progression of physical disability.
When attacks do occur, they tend to be shorter and
less severe. In addition, MRI scans suggest that
beta interferon can decrease myelin destruction.
Investigators speculate that the effects of beta
interferon may be due to the drug's ability to
correct an MS-related deficiency of certain white
blood cells that suppress the immune system and/or
its ability to inhibit gamma interferon, a substance
believed to be involved in MS attacks. Alpha
interferon is also being studied as a possible
treatment for MS. Common side effects of interferons
include fever, chills, sweating, muscle aches,
fatigue, depression, and injection site reactions.
Scientists continue their extensive efforts to
create new and better therapies for MS. Goals of
therapy are threefold: to improve recovery from
attacks, to prevent or lessen the number of relapses,
and to halt disease progression. Some therapies
currently under investigation are discussed below.
Immunotherapy
As evidence of immune system involvement in
the development of MS has grown, trials of
various new treatments to alter or suppress
immune response are being conducted. Most of
these therapies are, at this time, still
considered experimental.
Results of recent clinical trials have
shown that immunosuppressive agents
and techniques can positively (if
temporarily) affect the course of MS;
however, toxic side effects often preclude
their widespread use. In addition,
generalized
immunosuppression leaves the patient
open to a variety of viral, bacterial, and
fungal infections.
Over the years, MS investigators have
studied a number of immunosuppressant
treatments. One such treatment,
Novantrone (mitoxantrone),
was approved by the FDA for the treatment of
advanced or chronic MS. Other therapies
being studied are cyclosporine (Sandimmune),
cyclophosphamide
(Cytoxan),
methotrexate,
azathioprine (Imuran),
and total lymphoid irradiation (a process
whereby the MS patient's lymph nodes are
irradiated with x-rays in small doses over a
few weeks to destroy lymphoid tissue, which
is actively involved in tissue destruction
in autoimmune diseases). Inconclusive and/or
contradictory results of these trials,
combined with the therapies' potentially
dangerous side effects, dictate that further
research is necessary to determine what, if
any, role they should play in the management
of MS. Studies are also being conducted with
the immune system modulating drug
cladribine (Leustatin).
Another potential
treatment for MS is monoclonal antibodies,
which are identical, laboratory-produced
antibodies that are highly specific for a
single antigen. They are injected into the
patient in the hope that they will alter the
patient's immune response. One monoclonal
antibody, natalizumab
(Tysabri), was
shown in clinical trials to significantly
reduce the frequency of attacks in people
with relapsing forms of MS and was approved
for marketing by the U.S. Food and Drug
Administration (FDA) in 2004. However, in
2005 the drug’s manufacturer voluntarily
suspended marketing of the drug after
several reports of significant adverse
events. In 2006, the FDA again approved
sale of the drug for MS but under strict
treatment guidelines involving infusion
centers where patients can be monitored by
specially trained physicians.
Another experimental
treatment for MS is plasma exchange, or
plasmapheresis.
Plasmapheresis
is a procedure in which blood is removed
from the patient and the blood plasma is
separated from other blood substances that
may contain antibodies and other
immunologically
active products. These other blood
substances are discarded and the plasma is
then transfused back into the patient.
Because its worth as a treatment for MS has
not yet been proven, this experimental
treatment remains at the stage of clinical
testing.
Bone marrow transplantation (a procedure
in which bone marrow from a healthy donor is
infused into patients who have undergone
drug or radiation therapy to suppress their
immune system so they will not reject the
donated marrow) and injections of venom from
honey bees are
also being studied. Each of these therapies
carries the risk of potentially severe side
effects.
Therapy to Improve Nerve
Impulse Conduction
Because the transmission of electrochemical messages
between the brain and body is disrupted in MS,
medications to improve the conduction of nerve
impulses are being investigated. Since demyelinated
nerves show abnormalities of potassium activity,
scientists are studying drugs that block the
channels through which potassium moves, thereby
restoring conduction of the nerve impulse. In
several small experimental trials, derivatives of a
drug called aminopyridine temporarily improved
vision, coordination, and strength when given to MS
patients who suffered from both visual symptoms and
heightened sensitivity to temperature. Possible side
effects of these therapies include paresthesias (tingling
sensations), dizziness, and seizures.
Therapies Targeting an Antigen
Trials of a synthetic form of myelin basic protein,
called copolymer I (Copaxone), were successful,
leading the FDA to approve the agent for the
treatmernt of relapsing-remitting MS. Copolymer I,
unlike so many drugs tested for the treatment of MS,
has few side effects, and studies indicate that the
agent can reduce the relapse rate by almost one
third. In addition, patients given copolymer I are
more likely to show neurologic improvement than
those given a placebo.
Investigators are also looking at the possibility
of developing an MS vaccine. Myelin-attacking T
cells were removed, inactivated, and injected back
into animals with experimental allergic
encephalomyelitis (EAE). This procedure results in
destruction of the immune system cells that were
attacking myelin basic protein. In a couple of small
trials scientists have tested a similar vaccine in
humans. The product was well-tolerated and had no
side effects, but the studies were too small to
establish efficacy. Patients with progressive forms
of MS did not appear to benefit, although relapsing-remitting
patients showed some neurologic improvement and had
fewer relapses and reduced numbers of lesions in one
study. Unfortunately, the benefits did not last
beyond two years.
A similar approach, known as peptide therapy, is
based on evidence that the body canmount an immune
response against the T cells that destroy myelin,
but this response is not strong enough to overcome
the disease. To induce this response, the
investigator scans the myelin-attacking T cells for
the myelin-recognizing receptors on the cells'
surface. A fragment, or peptide, of those receptors
is then injected into the body. The immune system "sees"
the injected peptide as a foreign invader and
launches an attack on any myelin-destroying T cells
that carry the peptide. The injection of portions of
T cell receptors may heighten the immune system
reaction against the errant T cells much the same
way a booster shot heightens immunity to tetanus. Or,
peptide therapy may jam the errant cells' receptors,
preventing the cells from attacking myelin.
Despite these promising early results, there are
some major obstacles to developing vaccine and
peptide therapies. Individual patients' T cells vary
so much that it may not be possible to develop a
standard vaccine or peptide therapy beneficial to
all, or even most, MS patients. At this time, each
treatment involves extracting cells from each
individual patient, purifying the cells, and then
growing them in culture before inactivating and
chemically altering them. This makes the production
of quantities sufficient for therapy extremely time
consuming, labor intensive, and expensive. Further
studies are necessary to determine whether universal
inoculations can be developed to induce suppression
of MS patients' overactive immune systems.
Protein antigen feeding is similar to peptide
therapy, but is a potentially simpler means to the
same end. Whenever we eat, the digestive system
breaks each food or substance into its primary "non-antigenic"
building blocks, thereby averting a potentially
harmful immune attack. So, strange as it may seem,
antigens that trigger an immune response when they
are injected can encourage immune system tolerance
when taken orally. Furthermore, this reaction is
directed solely at the specific antigen being fed;
wholesale immunosuppression, which can leave the
body open to a variety of infections, does not occur.
Studies have shown that when rodents with EAE are
fed myelin protein antigens, they experience fewer
relapses. Data from a small, preliminary trial of
antigen feeding in humans found limited suggestion
of improvement, but the results were not
statistically significant. A multi-center trial is
being conducted to determine whether protein antigen
feeding is effective.
Cytokines
As our growing insight into the workings of the
immune system gives us new knowledge about the
function of cytokines, the powerful chemicals
produced by T cells, the possibility of using them
to manipulate the immune system becomes more
attractive. Scientists are studying a variety of
substances that may block harmful cytokines, such as
those involved in inflammation, or that encourage
the production of protective cytokines.
A drug that has been tested as a depression
treatment, rolipram, has been shown to reduce levels
of several destructive cytokines in animal models of
MS. Its potential as a therapy for MS is not known
at this time, but side effects seem modest. Protein
antigen feeding, discussed above, may release
transforming growth factor beta (TGF), a protective
cytokine that inhibits or regulates the activity of
certain immune cells. Preliminary tests indicate
that it may reduce the number of immune cells
commonly found in MS patients' spinal fluid. Side
effects include anemia and altered kidney function.
Interleukin 4 (IL-4) is able to diminish
demyelination and improve the clinical course of
mice with EAE, apparently by influencing developing
T cells to become protective rather than harmful.
This also appears to be true of a group of chemicals
called retinoids. When fed to rodents with EAE,
retinoids increase levels of TGF and IL-4, which
encourage protective T cells, while decreasing
numbers of harmful T cells. This results in
improvement of the animals' clinical symptoms.
Remyelination
Some studies focus on strategies to reverse the
damage to myelin and oligodendrocytes (the
cells that make and maintain myelin in the central
nervous system), both of which are destroyed during
MS attacks. Scientists now know that
oligodendrocytes may proliferate and form new myelin
after an attack. Therefore, there is a great deal of
interest in agents that may stimulate this reaction.
To learn more about the process, investigators are
looking at how drugs used in MS trials affect
remyelination. Studies of animal models indicate
that monoclonal antibodies and two immunosuppressant
drugs, cyclophosphamide and azathioprine, may
accelerate remyelination, while steroids may inhibit
it. The ability of intravenous immunoglobulin (IVIg)
to restore visual acuity and/or muscle strength is
also being investigated.
Diet
Over the years, many people have tried to implicate
diet as a cause of or treatment for MS. Some
physicians have advocated a diet low in saturated
fats; others have suggested increasing the patient's
intake of linoleic acid, a polyunsaturated fat, via
supplements of sunflower seed, safflower, or evening
primrose oils. Other proposed dietary "remedies"
include megavitamin therapy, including increased
intake of vitamins B12 or C; various liquid diets;
and sucrose-, tobacco-, or gluten-free diets. To
date, clinical studies have not been able to confirm
benefits from dietary changes; in the absence of any
evidence that diet therapy is effective, patients
are best advised to eat a balanced, wholesome diet.
Unproven Therapies
MS is a disease with a natural tendency to remit
spontaneously, and for which there is no universally
effective treatment and no known cause. These
factors open the door for an array of
unsubstantiated claims of cures. At one time or
another, many ineffective and even potentially
dangerous therapies have been promoted as treatments
for MS. A partial list of these "therapies" includes:
injections of snake venom, electrical stimulation of
the spinal cord's dorsal column, removal of the
thymus gland, breathing pressurized (hyperbaric)
oxygen in a special chamber, injections of beef
heart and hog pancreas extracts, intravenous or oral
calcium orotate (calcium EAP), hysterectomy, removal
of dental fillings containing silver or mercury
amalgams, and surgical implantation of pig brain
into the patient's abdomen. None of these treatments
is an effective therapy for MS or any of its
symptoms.
Are Any MS Symptoms Treatable?
While some scientists look for therapies that will
affect the overall course of the disease, others are
searching for new and better medications to control
the symptoms of MS without triggering intolerable
side effects.
Many people with MS have problems with
spasticity, a condition that primarily
affects the lower limbs. Spasticity can occur either
as a sustained stiffness caused by increased muscle
tone or as spasms that come and go, especially at
night. It is usually treated with muscle relaxants
and tranquilizers. Baclofen (Lioresal), the most
commonly prescribed medication for this symptom, may
be taken orally or, in severe cases, injected into
the spinal cord. Tizanidine (Zanaflex), used for
years in Europe and now approved in the United
States, appears to function similarly to baclofen.
Diazepam (Valium), clonazepam (Klonopin), and
dantrolene (Dantrium) can also reduce spasticity.
Although its beneficial effect is temporary,
physical therapy may also be useful and can help
prevent the irreversible shortening of muscles known
as contractures. Surgery to reduce spasticity is
rarely appropriate in MS.
Weakness and ataxia
(incoordination) are also characteristic of MS. When
weakness is a problem, some spasticity can actually
be beneficial by lending support to weak limbs. In
such cases, medication levels that alleviate
spasticity completely may be inappropriate. Physical
therapy and exercise can also help preserve
remaining function, and patients may find that
various aids-such as foot braces, canes, and walkers-can
help them remain independent and mobile.
Occasionally, physicians can provide temporary
relief from weakness, spasms, and pain by injecting
a drug called phenol into the spinal cord, muscles,
or nerves in the arms or legs. Further research is
needed to find or develop effective treatments for
MS-related weakness and ataxia.
Although improvement of optic symptoms
usually occurs even without treatment, a short
course of treatment with intravenous
methylprednisolone (Solu-Medrol) followed by
treatment with oral steroids is sometimes used. A
trial of oral prednisone in patients with visual
problems suggests that this steroid is not only
ineffective in speeding recovery but may also
increase patients' risk for future MS attacks.
Curiously, prednisone injected
directly into the veins-at ten times the oral dose-did
seem to produce short-term recovery. Because of the
link between optic neuritis and MS, the study's
investigators believe these findings may hold true
for the treatment of MS as well. A follow-up study
of optic neuritis patients will address this and
other questions.
Fatigue, especially in the legs,
is a common symptom of MS and may be both physical
and psychological. Avoiding excessive activity and
heat are probably the most important measures
patients can take to counter physiological fatigue.
If psychological aspects of fatigue such as
depression or apathy are evident, antidepressant
medications may help. Other drugs that may reduce
fatigue in some, but not all, patients include
amantadine (Symmetrel), pemoline (Cylert), and the
still-experimental drug aminopyridine.
People with MS may experience several types of
pain. Muscle and back pain can be
helped by aspirin or acetaminophen and physical
therapy to correct faulty posture and strengthen and
stretch muscles. The sharp, stabbing facial pain
known as trigeminal neuralgia is commonly treated
with carbamazapine or other anticonvulsant drugs or,
occasionally, surgery. Intense tingling and burning
sensations are harder to treat. Some people get
relief with antidepressant drugs; others may respond
to electrical stimulation of the nerves in the
affected area. In some cases, the physician may
recommend codeine.
As the disease progresses, some patients develop
bladder malfunctions. Urinary
problems are often the result of infections that can
be treated with antibiotics. The physician may
recommend that patients take vitamin C supplements
or drink cranberry juice, as these measures acidify
urine and may reduce the risk of further infections.
Several medications are also available. The most
common bladder problems encountered by MS patients
are urinary frequency, urgency, or incontinence. A
small number of patients, however, retain large
amounts of urine. In these patients, catheterization
may be necessary. In this procedure, a catheter or
drainage tube is temporarily inserted (by the
patient or a caretaker) into the urethra several
times a day to drain urine from the bladder. Surgery
may be indicated in severe, intractable cases.
Scientists have developed a "bladder pacemaker" that
has helped people with urinary incontinence in
preliminary trials. The pacemaker, which is
surgically implanted, is controlled by a hand-held
unit that allows the patient to electrically
stimulate the nerves that control bladder function.
MS patients with urinary problems may be
reluctant to drink enough fluids, leading to
constipation. Drinking more water and
adding fiber to the diet usually alleviates this
condition. Sexual dysfunction may
also occur, especially in patients with urinary
problems. Men may experience occasional failure to
attain an erection. Penile implants, injection of
the drug papaverine, and electrostimulation are
techniques used to resolve the problem. Women may
experience insufficient lubrication or have
difficulty reaching orgasm; in these cases, vaginal
gels and vibrating devices may be helpful.
Counseling is also beneficial, especially in the
absence of urinary problems, since psychological
factors can also cause these symptoms. For instance,
depression can intensify symptoms
of fatigue, pain, and sexual dysfunction. In
addition to counseling, the physician may prescribe
antidepressant or antianxiety medications.
Amitriptyline is used to treat laughing/weeping
syndrome.
Tremors are often resistant to
therapy, but can sometimes be treated with drugs or,
in extreme cases, surgery. Investigators are
currently examining a number of experimental
treatments for tremor.
Drugs Used to Treat Symptoms of Multiple
Sclerosis
|
Symptom |
Drug |
|
Spasticity |
Baclofen
(Lioresal)
Tizanidine (Zanaflex)
Diazepam (Valium)
Clonazepam (Klonopin)
Dantrolene (Dantrium) |
|
Optic neuritis |
Methylprednisolone (Solu-Medrol)
Oral
steroids |
|
Fatigue |
Antidepressants
Amantadine (Symmetrel)
Pemoline (Cylert) |
|
Pain |
Aspirin or
acetaminophen
Antidepressants
Codeine |
|
Trigeminal
neuralgia |
Carbamazapine,
other anticonvulsant |
|
Sexual
dysfunction |
Papaverine
injections(in men) |
National Institute of Neurological
Disorders and Stroke (NINDS)
National Institutes of Health
Brain Resources and Information Network
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