Re: Re: News on a New MS Pill instead of injection?

Dear Ana,

As a neuroscientist working in the field of neurodegenerative 
disorders I can assure you that soon there will be some definitive 
and more  promising cure for this disease. Intensive research is 
underway to study a variety of promising new drugs. Currently, 
treatment is aimed at maintaining a maximum quality of life and 
several drugs have proven to be effective. Physiotherapy can also 
play an important role. Here, i’ve given the overview of some of the 
treatments available and their general mechanism of action. I have 
elaborated a bit on Copaxone as this is the medication which you are 
taking. Apart from this there at the end i have mentioned about the 
two most recent drugs under final stage of clinical trials, showing very 
promising results. The interesting thing about them is that they can 
be administered orally, which will reduce some pain and stress 
involved with daily/weekly injections.

There are three primary forms of medication used to treat the 
symptoms:

    * During an exacerbation, corticosteroids (such as prednisone or 
methylprednisolone) used at high dosages (500 mg–2 g per day 
intravenously for a course of 3 to 5 days) can accelerate regression of 
symptoms.There is no good evidence that corticosteroids influence 
longterm outcome.

 Long-term treatment can influence the course of the disease:

          o Interferon beta-1a or beta-1b (Avonex; Betaseron [in Europe 
Betaferon]; Rebif) has been shown to reduce the relapse rate by 
about 30%, decrease the number of new MRI lesions and slow 
progression of disability. Interferon-beta is a cytokine that under 
natural conditions is produced by the body during viral infections; as 
a drug it is extracted either from special mammalian cells or special 
bacteria. All preparations must be injected into either muscle or skin 
every second day to once per week, depending on the preparation. 
Attempts to develop pills containing Interferon-beta have not been 
successful so far. Some of the interferons have been proven to be 
effective not only in relapsing remitting MS, but also in secondary 
progressive MS.

          o Glatiramer acetate (Copaxone) has also been shown to 
reduce the relapse rate by about 30%, decrease the number of new 
MRI lesions and slow progression of disability. Concerning its 
therapeutic effect it is approximately   comparable  to Interferon-beta. 
Glatiramer acetate  consists of synthetic peptides made of four 
different amino acids, which are basic modules of all proteins in the 
human body. Once per day must be injected into the skin. Attempts to 
develop pills containing glatiramer acetate have also been 
unsuccessful. Copaxone is effective in the treatment of relapsing 
remitting MS. So far, beneficial effects in secondary progressive MS 
have not been convincingly demonstrated.  
Main side effects include inflammatory skin reactions at the injection 
site, and a rare but transient and perturbing "post-injection" reaction 
manifested by flushing, chest tightness, heart palpitations, 
breathlessness, and anxiety. A post-injection reaction does not 
require discontinuation of therapy. In general, Copaxone is 
considered to cause fewer side effects than Interferon-beta. Regular 
blood monitoring is required.

          o Azathioprine is an agent available as a pill approved for the 
treatment of relapsing remitting MS in some countries. However, its 
effectiveness has not been proven as stringently as for the 
interferons and glatiramer acetate, and an effect in secondary 
progressive MS has not been demonstrated. In general, it is well 
tolerated. After longtime therapy the risk of cancer increases slightly 
(after 10 years of therapy about fourfold). 

          o Low-dose-naltrexone (LDN) has been reported to reduce the 
rate of progression and relapse rate in MS, however evidence is so 
far principally based on patient reports and no formal studies have 
confirmed its effectiveness so far (as of 2005). It is believed to 
operate by stimulating immune response, which works in the 
opposite manner to the beta interferons, so using both together is 
considered unlikely to produce positive results.
     
          o The currently most effective drug in the preventive treatment of 
MS is Mitoxantrone. It has been proven to be effective in relapsing 
remitting and in secondary progressive  MS. In most cases it is 
administered every three months intravenously. Therapy with 
Mitoxantrone is generally well tolerated, however, since with ongoing 
therapy the risk for damage of the heart muscle increases, at an 
average Mitoxantrone can only be administered for 3 to 4 years. This 
is why Mitoxantrone is only used in cases of rapid disease 
progression. 

          o A recent study found that women who took vitamin D 
supplements were 40% less likely to develop multiple sclerosis than 
women who did not take supplements. However, this study does not 
provide enough data to conclude that vitamin D has a beneficial 
influence on ongoing MS. Furthermore it could not distinguish 
between a beneficial effect of vitamin D and multivitamin drugs 
including vitamin E and various B vitamins which may also exert a 
protective effect.

    * A variety of medications are used to treat symptoms without 
influencing the inflammatory nature of the disease (symptomatic 
treatment):
          
 	        o Baclofen and tizanidine can be useful against spasticity.

          o The anticonvulsant drugs Gabapentin and Carbamazepine 
and the antidepressant amitriptyline can improve pain and tingling 
sensations in certain cases.

          o SSRIs (Selective Seretonin Release Inhibitors) be used for 
depression, as well as for fatigue. Fatigue can also be influenced by 
amantadine and modafinil.

          o There is also treatment for bladder disturbances available 
which is effective in many cases. Examples are oxybutynin and 
trospium chloride.

          o Treatment with sildenafil (Viagra®) or similar substances can 
improve male erectile dysfunction in many cases.

Additional treatment options include plasmapheresis ("washing the 
blood", showing similarities to dialysis) for severe, non-steroid 
responsive relapses.


Recently two different oral therapies for multiple sclerosis have 
shown positive results in preliminary Phase 2 clinical trials.

FTY720

FTY720 is a once-daily oral medication, developed by Novartis 
Pharma and licensed from Mitsubishi Pharma Corporation. This drug 
with its novel mode of action offers the potential of an innovative 
approach to MS treatment. 

Mechanism of action:
FTY720 is the first sphingosine-1-phosphate (S1P) receptor 
modulator. FTY720 differs from currently approved treatments 
because it is the only medication that binds the receptors of S1P, 
present on the surface of lymphocytes, which are a subpopulation of 
white blood cells. In MS,  lymphocytes circulating in the central 
nervous system (e.g. the brain and spinal cord) attack the myelin 
sheath that surrounds and protects nerve fibers (axons) which are 
responsible for transmitting nerve signals to other parts of the body. 
As a consequence of receptor binding, the lymphocytes can no 
longer respond to the molecule that signals them to circulate to sites 
of inflammation in the body and they stay in the lymph nodes. 
However, the lymphocytes remain functional and may still be 
activated within the lymph nodes as part of the immune response. 

FTY720 has shown a significant and consistent effect on both clinical 
relapses and MRI measures in just six months. Based on the 
positive Phase II study results, Novartis is currently discussing with 
regulatory authorities the FTY720 Phase III program which is 
expected to be launched in the fourth quarter of 2005 involving 
centers in North America and Europe. With its novel mode of action 
and the added benefit of an oral formulation taken once daily, further 
clinical development of FTY720 might have a major impact on the 
way MS is treated in future.

Temsirolimus

Temsirolimus is another oral medication, developed Wyeth 
Pharmaceuticals.This drug blocks the proliferation of immune T cells 
activated by the immune messenger protein called interleukin 2. 
Such T cells are thought to play a role in the immune attack against 
the nervous system that underlies MS.
The promising findings from short-term study suggest that further 
clinical testing of this oral drug for MS is warranted. At this time, 
Wyeth has not made public any plans for further Phase 3 testing.

Well, if you have further queries feel free to contact me. If the above 
summary doesn’t anwer you question you can return back to me 
again with more specific questions. Also, if my answer doesn’t 
include the drug about which you wanted to know, then you can name 
it and then i can inform you more about it.

Best wishes!!

Amit

References: 
http://www.m
strust.org.uk/news/msonthenet.jsp
 ht
tp://www.msif.org/en/ms_the_disease/demyelination.html
 http://www.nationalmssocie
ty.org/
 http://medlineplus.gov/