(FTY720) has the option of being the
first orally available drug against MS. In
1994, an immunosuppressive natural product, ISP-I (myriocin), was
the culture broth of Isaria sinclairii, a type of vegetative wasp. The
modification of ISP-I yielded a new compound, FTY720, which has more
immunosuppressive activity and less toxicity . This
that becomes phosphorylated in vivo and acts as a
(S1P) receptor agonist  - which may be clear to a few specialists.
the World, it is perhaps better understandable that the drug has
shown to reduce inflammatory activity by an effect on the macrophages.
striking feature of Fingolimod is also the induction of a marked
peripheral blood T- and B-cells .
As an immunosuppressive, the drug is being tested on a number of
clinical indications, such as transplantion surgery and a variety of
autoimmune diseases. It does not impair T and B lymphocytes but
interferes with the re-circulation of lymphocytes between
lymphoid organs and blood . This action has established S1P
receptors as key targets for future drug development.
We have, since the introduction of the beta-interferonn [ns, witnessed
number of therapies with some effect upon MS - and still the long-term
have largely been disappointing. We have learned to be cautious with
euphoria. What justifies new hopes related to this drug is first of all
experimental efficacy. Again, the experimental autoimmune
(EAE) seems to be a condition in which mice may profit from anything,
with cheese. In such a placebo-controlled study , however, the
FTY720-treated animals displayed no signs of inflammatory activity or
neurological impairment - 100% vs 0% effect.
In the first study on humans , involving 281 patients (of whom 255
6 months and 227 one year), the number of gadolinium-enhanced
relapse rates remained low in the therapy groups. The low-dose (1,25 mg
group was slightly favorable to the high dose (5 mg
daily) group. In a study of oral vs. IV administration, the mean
lymphocyte nadir was 35% lower after oral than after IV administration
of 1.25 mg orally and 1 mg IV .
As usual, the therapy was compared to placebo and not to the other
that neurologists have previously claimed to be effective the
MS (A Conflict to Come). Despite this
ethical problem, I share the hope for
this substance in the coming years.
Brinkmann  reported that
the drug may act through
immune-based and central mechanisms to reduce
inflammation and support structural restoration of the central nervous
parenchyma," and thus not be confined simply to reduce relapse
rates. The mode of action was further described by Chun and Hartung
, who reported that "Fingolimod-phosphate
activates lymphocyte S1P1 via
high-affinity receptor binding yet subsequently induces S1P1
that prevents lymphocyte egress from lymphoid tissues, thereby reducing
autoaggressivelymphocyte infiltration into the central nervous system."
The clinical studies remained positve in their conclusions. In a large (>1000 patients for 24 months)
study, Kappos et al.  found that, “As compared with placebo, both
1.25 mg] doses of oral fingolimod improved the relapse rate, the risk
disability progression, and end points on MRI.”In a 12-months study of more than 1000 patients (and
comparatively many aurthors and "collaborators"),
the drug was finally tested towards another classical MS drug. The
found “superior efficacy of oral fingolimod with respect to relapse
MRI outcomes in patients with multiple sclerosis, as compared with
intramuscular interferon beta-1a.“ However, “Two fatal infections
the group that received the 1.25-mg dose of fingolimod,” a dose now
while it probably increases the risk of adverse effects without
offering more success than 0.5 mg.Other adverse effects include bradycardia and
atrioventricular block, increased liver enzyme levels, hypertension and
has convinced further in 2011. Simultaneously,
one must regret that this is one of the most expensive oral therapies
available. So far (June 2011), I found no new studies addressing
efficacy of fingolimod this year. Johnson et al.  found that time
lymphocyte reconstitution after prolonged FTY720 therapy can be
greater than predicted by shorter-term studies. Our current knowledge
drug’s metabolismwas summarized by
Zollinger et al. . Mehling et al.  found that
individuals can mount vaccine-specific adaptive immune responses
healthy controls. Kowarik et al.  found that fingolimod exerts a
differential effect on various WCB cells of importance in MS
P, Foster CA, Baumann DR, Cannet
C, Rudin M. Predictability of FTY720 efficacy in experimental
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