Multiple Sclerosis:

Multiple sclerosis is an autoimmune
disease that affects the brain and
spinal cord (central nervous system).
An autoimmune disorder is a condition
that occurs when the immune system
mistakenly attacks and destroys
healthy body tissue. There are more
than 80 different types of autoimmune
disorders.

Multiple sclerosis (MS) is a potentially
debilitating disease in which the body's
immune system eats away at the
protective sheath that covers the
nerves. This interferes with the
communication between the brain and
the rest of the body. Ultimately, this
may result in deterioration of the
nerves themselves, a process that's
not reversible.

In August 2011 a new study have
discovered 29 new genetic variations
linked to multiple sclerosis, with many
involving genes relevant to the immune
system – a finding that they say
bolsters the theory that MS is a
primarily an autoimmune disease.

The new study, published  in the
journal Nature, is the largest-ever
study on the genetics of multiple
sclerosis. More than 250 scientists
collaborated on the work, and close to
10,000 MS patients were involved.

Many of the gene variations the team
discovered are involved in the
development of the immune system's T-
cells, which are the immune cells that
protect against infections. When T-
cells become "confused," they trigger
autoimmune diseases that mistake
healthy body tissues as foreign and
attack them.

By scrutinizing up to 20 billion genetic
clues in the DNA of more than 40,000
people, including many with multiple
sclerosis, they have more than
doubled the number of genes
contributing to the disease.

The largest genetics-based study of
multiple sclerosis ever conducted is
casting significant doubt on a
controversial theory that the disease is
a vascular condition caused by
blocked neck veins.

The study identified more than two
dozen new genetic variants common to
people with MS and found the majority
of genes involved are pivotal to the
immune system.

The discovery strongly suggests MS
originates as an inflammatory immune
response and casts aside “eccentric
and maverick ideas” that it is caused
by venous abnormalities, said Alastair
Compston, neurology professor at the
University of Cambridge and a joint
lead author of the study.

“One can say that this provides
absolutely no support whatsoever for
that [blocked veins] idea,” Prof.
Compston said.

The study is sure to stoke debate in
Canada’s MS community, where many
patients and researchers are divided
over the controversial theory made
popular by Paolo Zamboni. The Italian
doctor believes MS is caused by
venous abnormalities, a theory that
has been seized upon by thousands of
patients across Canada who have
flown to expensive overseas clinics for
treatment of blocked veins.

Proponents of the Zamboni theory
have used social media to pressure
politicians into bringing the unproven
treatment to Canada. The federal
government recently announced it will
invest funds in a clinical trial of the
procedure.

Nearly 250 researchers working as
part of a major international
consortium found 29 new genetic
variants common to MS and confirmed
that 23 previously identified genetic
associations are linked to the disease.

In addition to playing a role in the
immune system, one-third of the genes
involved in the research are also
linked to other autoimmune conditions,
including Type 1 diabetes, rheumatoid
arthritis and Crohn’s disease. The
findings were in the journal Nature.

While the discovery is important, the
large number of genes implicated in
MS also indicates how complex it is
and how much more work remains to
be done.

Multiple sclerosis occurs when ‘friendly
fire' from the body's immune system,
destroys myelin, the fatty protective
sheath around nerve fibres in the brain
and spinal cord, disrupting the
transmission of signals vital to
everything from seeing and walking to
thinking and bladder control.



BIOGEN'S BG-12
In October 2011 shares of Biogen Idec
gained 6% in one day  after the
biotech firm released positive Phase III
clinical data for its multiple sclerosis
drug BG-12. Many biotech watchers
believe that if it were to win regulatory
approval, BG-12 could become a
major product for the company
because it is administered orally. In
comparison, most of the leading
treatments for MS currently on the
market are either injected or delivered
through an IV.

The study, which tested doses of
240mg twice a day and three times a
day, found both dosage levels cut the
relapse rate in half.

BG-12 is the leading candidate to
compete with Gilenya, the blockbuster
drug launched in the U.S. in 2010 by
Novartis.  Gilenya was the first oral
treatment for a disease that had
previously been treated with a regime
of injections.



QUESTCOR'S ACTHAR
In October 2011 the North American
Research Committee on Multiple
Sclerosis released a survey of 2,000
MS patients who suffered relapses,
and found that 31% of them did not
respond to the traditional treatment of
corticosteroids. That's bad news for
the patients, but good news for
Questcor Pharmaceuticals (QCOR),
whose lone drug, Acthar, is approved
for exactly that purpose.




NOVARTIS'S  GILENYA   FOR
MULTIPLE SCLEROSIS
In August 2011 the UK health-care
watchdog, NICE  recommended
against reimbursing for Novartis AG's
multiple-sclerosis medicine Gilenya
because of uncertainties over the
drug's clinical effectiveness for certain
patients.

Gilenya, which has been approved in
the U.S., Europe and elsewhere, is one
of Novartis's most promising
medicines, expected to reach annual
peak sales of more than $3 billion. The
high price of the pill—more than
$40,000 per patient per year—has
been considered justified because it is
easier to use than standard treatments
that require injections or infusions.

Gilenya is the first approved oral
treatment indicated for relapsing forms
of MS in the US, a major advance for
people with this disease.

Gilenya showed superior efficacy by
reducing relapses by 52% at one year
compared with interferon beta-1a IM, a
commonly prescribed treatment.

Two-year, placebo-controlled study
showed that Gilenya significantly
reduced the risk of disability
progression.

It has a well-studied safety and
tolerability profile with over 2,600
clinical trial patients.

Gilenya competes  with injectibles from
Biogen Idec, Bayer, Merck KGaA, and
Teva Pharmaceuticals.

In June 2011  Merck KGaA of Germany
abandoned attempts to market a rival
treatment.

That means Novartis has the only oral
multiple-sclerosis treatment in the
market at the moment.

Currently, Teva and its marketing
partner Sanofi-Aventis (SNY) lead the
market with Copaxone, which had more
than $2.8 billion in sales in 2009.
Biogen's Avonex raked in more than
$2 billion as well, and the other drugs
in the category managed to draw sales
over $1 billion each. The side effects
for these drugs can often be severe
and the inconvenience and pain that
comes from daily injections are
unwelcome to many patients. Some
analysts estimate that the market could
expand rapidly if an oral medication is
available just adding those patients
that couldn’t handle the side effects or
pain of the injectibles.



DR ZAMBONI'S PIONEERING THEORY
REGARDING MULTIPLE SCLEROSIS
Italian doctor Paolo Zamboni believes
MS symptoms stem from abnormal
blood flow out of the brain  and can be
alleviated by angioplasty but not  
necessarily by using stents.
It is proposed that insufficient venous
blood flow (Chronic cerebro-spinal
venous insufficiency (CCSVI),
promotes development of brain
dysfunction, especially multiple
sclerosis.

A new trial has started testing the
theory:
It is hypothesized that the narrowing in
the large veins in the neck and chest
might cause improper drainage of
blood from the brain, resulting in
eventual injury to brain tissue. It is
thought that angioplasty -- treatment
commonly used by cardiologists and
other endovascular surgeons to treat
atherosclerosis -- may remedy the
blockages.

Zamboni has conducted preliminary
studies that suggest the efficacy of
venous angioplasty - "liberation
procedure" -- in the amelioration of MS
symptoms.

In April 2011 a new University of
Buffalo study suggested  that chronic
cerebral venous insufficiency (CCSVI),
which is a blocking or narrowing of
extracranial veins that some
researchers claim causes MS
symptoms, may be a result of MS and
not a cause.

Canadians suffering from MS have
travelled abroad to Bulgaria, Poland,
Mexico and other countries for the
controversial liberation therapy
procedure, which involves opening
blocked veins in the neck. The
procedure, developed by Zamboni, is
banned in Canada because it is not
scientifically supported.



August  2011 UPDATE:

DACLIZUMAB
Biogen and Abbott’s multiple sclerosis
drug daclizumab has performed well in
a mid-stage trial, but two deaths
marred the overall results.

The phase IIb study involved patients
receiving daclizumab high-yield
process (or DAC HYP), an injection
which needs to be given just once
every four weeks.

Biogen is a lead player in multiple
sclerosis - Avonex leads the beta
interferon market with $2.5 billion in
sales, while Tysabri (natalizumab), is
co-marketed with Elan and earned
$1.2 billion last year.

Biogen and Abbott hope the greater
convenience of the new injectable,
twinned with good efficacy can help it
maintain its dominant market position,
but competition is hotting up.  

Biogen Idec Inc. and Abbott
Laboratories in August 2011 reported
positive data from experimental once-
monthly multiple sclerosis drug
daclizumab HYP.

The results are the first step in
bringing the drug to market. A second
required trial isn't likely to bring data
for at least two years. The latest study
shows that daclizumab HYP seems to
be more effective than many commonly
used MS treatments, but some
questions remain about its side effects
and how it will fit in an increasingly
competitive market.

Convenience is a factor in the
attraction of daclizumab HYP, which is
given once a month by subcutaneous
injection compared with once-weekly
and once-daily injections for popular
MS treatments. Although the
improvement is notable, it will have to
compete with the emerging market for
oral MS therapies, thought to be the
most attractive to patients.



COMPETITION:
The recent arrival of Novartis’ oral
drug Gilenya (fingolimod) has changed
the dynamic of the market, and two
other rival oral drugs, Sanofi’s
Lemtrada (alemtuzumab) and Teva’s
laquinimod, are expected to be filed in  
2012.



LEMTRADA/ CAMPATH-1H  DRUG
TESTED FOR MULTIPLE SCLEROSIS
In an initial study, more than 60
patients have been treated by doctors
at Addenbrooke's Hospital in
Cambridge,UK  with some very
impressive results. After five days of
treatment with LEMTRADA/ CAMPATH-
1H, the occurrence of new brain
lesions was greatly reduced for many
years.

This has now progressed to a phase III
clinical trial (sponsored by Genzyme
Inc./Sanofi) comparing two short
courses of CAMPATH-1H a year apart
with standard beta-interferon injections
in relasping remitting MS patients.
Analysis of the results at 3 years
indicated that CAMPATH-1H treatment
reduced the risk of accumulating
disability by 70% compared to beta
inteferon treatment.

Campath-1H is a potentially new
treatment for Multiple Sclerosis.  It is
currently (2011) undergoing trials in
the UK, USA, Italy and Croatia to
determine whether it can help those
with an early form of MS. The drug is a
monoclonal antibody designed to
target that part of the immune system
which is assumed to be harming
people with MS. Campath's scientific
name is alemtuzumab and it is
currently manufactured by ILEX
Pharmaceuticals and distributed by
Berlex Laboratories. It has been
developed for a number of years, and
has already been used as a treatment
for B-cell chronic lymphocytic leukemia.


OTHER DEVELOPMENTS

LAQUINIMOD BY TEVA MAY BE DEAD
In July 2011 Teva Pharmaceutical
Industries Ltd. ’s experimental multiple
sclerosis pill failed to reduce relapses
more than placebo in a clinical trial,
dealing a blow to the company’s effort
to find a successor to an older drug.

A previous late-stage trial, Allegro,
showed that laquinimod worked. The
drug reduced relapses by 23 percent
compared with a placebo and cut
disability progression by 36 percent,
Teva said in April 2011.

The FDA requires two successful late-
stage clinical trials before approving
MS drugs, so a third study is likely to
be necessary.

Teva already sells the multiple
sclerosis drug Copaxone, which it says
is the most prescribed MS drug in the
world.



STEM CELL TRIAL
The British press was  abuzz in August
2011 about a new planned trial to test
a stem cell therapy in patients with
multiple sclerosis.

The study is reportedly set to begin
later in 2011 and will involve more than
100 patients around the globe. The
plan is to harvest stem cells from the
bone marrow of participants, grow
them in a lab, and then implant them in
MS patients.



SAVITEX, A LEGAL DRUG  FROM
MARIJUANA FOR MULTIPLE
SCLEROSIS
Savitex was approved in Germany in
May 2011 for multiple sclerosis.
It is a  drug manufactured from
cannabis (marijuana) and used as a  
spray for treatment of spasticity.

Spasticity is  muscle stiffness that  is a
common symptom of MS affecting
about 80% of the 130,000 MS patients
in Germany.

Sativex is a first in class
endocannabinoid system modulator
and is delivered by an oromucosal
spray  which is sprayed into the mouth
either onto the inside of the cheek or
under the tongue.

Sativex offers the first new therapeutic
option in decades to patients in
Germany who have previously failed to
respond adequately to other anti-
spasticity medication. The spray is
quickly absorbed through the oral
mucosa, is easy to use for patients
and enables them to optimally adjust
their dosage. The medicine is already
available for MS patients in the UK and
Spain. It is made by GW Pharma Plc,
UK.