Neuromuscular Diseases: Focus on Multiple Sclerosis, Amyotrophic Lateral Sclerosis, and Muscular Dys

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Neuromuscular Diseases Focus on Multiple
Sclerosis, Amyotrophic Lateral Sclerosis, and
Muscular Dystrophy

• 9.20 - 9.30 Introduction to the session
• 9.30 - 10.15 Alex KAZANTSEV Massachusetts
  General Hospital, Harvard Medical School,
  Charlestown, MA (USA) Multiple and Amyotrophic
  Lateral Sclerosis Understanding the Mechanisms
  of Neurodegeneration and Developing Diverse
  Therapeutics
• 10.15 - 11.00 John MATSOUKAS - University of
  Patras, Patras (Gr)Linear and Cyclic Myelin
  Analogues in the Immunotherapy of Multiple
  Sclerosis
• 11.30 - 12.15 Rebecca PRUSS - TROPHOS, Marseille
  (F)Use of Cell Based Assays to Define SAR and
  Select Drug Candidates for Motor Neuron Diseases
  (and Other Indications)
• 15.00 - 15.45 Pier Lorenzo PURI - Burnham
  Institute, San Diego (USA) e Dulbecco Telethon
  Institute, S. Lucia/EBRI , Rome (I)Epigenetic
  Basis of Muscle Regeneration in Muscular
  Dystrophy
• 15.45 - 16.30 Carlo GAETANO - IDI, Rome (I) NO
  Sparks off Chromatin Tale of a Multifaceted
  Epigenetic Regulator

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What is Multiple Sclerosis?
Multiple sclerosis (or MS) is a chronic, often
disabling disease That attacks the central
nervous system (CNS), which is made up of the
brain, spinal cord, and optic nerves. Symptoms
may be mild, such as numbness in the limbs, or
severe, such as paralysis or loss of vision.
The progress, severity, and specific symptoms
of MS are unpredictable and vary from one person
to another. Today, new treatments and advances
in research are giving new hope to people
affected by the disease.
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MS is Thought to be an Autoimmune Disease
The bodys own defense system attacks myelin, the
fatty substance that surrounds and protects the
nerve fibers in the central nervous system. The
nerve fibers themselves can also be damaged. The
damaged myelin forms scar tissue (sclerosis),
which gives the disease its name. When any part
of the myelin sheath or nerve fiber is damaged
or destroyed, nerve impulses traveling to and
from the brain and spinal cord are distorted or
interrupted, producing the variety of symptoms
that can occur.
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Treatments for MS
Although there is still no cure for MS, effective
strategies are available to modify the disease
course, treat exacerbations (also called attacks,
relapses, or flare-ups), manage symptoms,
improve function and safety, and provide
emotional support. In combination, these
treatments enhance the quality of life for
people living with MS.
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Glatiramer acetate
Glatiramer acetate is a random polymer (average
molecular mass 6.4 kD) composed of four amino
acids that are found in myelin basic protein. It
is an immunomodulator, licensed in much of the
world for reduced frequency of relapses in
relapsing-remitting multiple sclerosis. It is a
non-interferon and non steroidal medication. The
mechanism of action for glatiramer is unknown,
although several have been proposed.
Glatiramer acetate
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Mitoxantrone
Mitoxantrone is a type II topoisomerase
inhibitor it disrupts DNA synthesis and DNA
repair in both healthy cells and cancer cells. It
also engages in intercalation.
It is used in the treatment of certain types of
cancer, mostly metastatic breast cancer, acute
myeloid leukemia, and non-Hodgkin's lymphoma.
mitoxantrone
Mitoxantrone is also used to treat multiple
sclerosis (MS), most notably the subset known as
secondary progressive MS. Mitoxantrone will not
cure multiple sclerosis, but is effective in
slowing the progression of secondary progressive
MS.
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What is ALS?
Amyotrophic lateral sclerosis (ALS) is a
progressive neurodegenerative disease that
affects nerve cells in the brain and the spinal
cord. Motor neurons reach from the brain to the
spinal cord and from the spinal cord to the
muscles throughout the body. The progressive
degeneration of the motor neurons in ALS
eventually leads to their death. When the motor
neurons die, the ability of the brain to
initiate and control muscle movement is lost.
With voluntary muscle action progressively
affected, patients in the later stages of the
disease may become totally paralyzed.
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Is There Any Treatment for ALS?
No cure has yet been found for ALS. However, the
FDA has approved the first drug treatment for
the diseaseriluzole.  Riluzole is believed to
reduce damage to motor neurons and prolongs
survival by several months, mainly in those with
difficulty swallowing.  Other treatments are
designed to relieve symptoms and improve the
quality of life for people with ALS.  Drugs also
are available to help individuals with pain,
depression, sleep disturbances, and
constipation.  Individuals with ALS may
eventually consider forms of mechanical
ventilation (respirators). 
riluzole
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Riluzole

• Riluzole has several actions
• Sodium channel blockade
• High-voltage calcium channel blockade
• N-methyl-D-aspartate (NMDA)/glutamate receptor
  antagonism
• Glutamate transporter activation
• Inhibition of protein kinase C
• Riluzole preferentially blocks TTX sensitive
  sodium channels, which are associated with
  damaged neurons. This reduces influx of calcium
  ions and indirectly prevents stimulation of
  glutamate receptors. Together with direct
  glutamate receptor blockade, the effect of the
  neurotransmitter glutamate on motor neurons is
  greatly reduced.

riluzole
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What Is Muscular Dystrophy?
Muscular dystrophy (MD) is a genetic disorder
that weakens the muscles that help the body
move. People with MD have incorrect or missing
information in their genes, which prevents them
from making the proteins they need for healthy
muscles. MD weakens muscles over time, so
children, teens, and adults who have the disease
can gradually lose the ability to do the things
most people  take for granted, like walking or
sitting up. Someone with MD might start having
muscle problems as a baby or their symptoms
might start later. Some people even develop MD
as adults. Duchenne muscular dystrophy (DMD),
the most common type of the disease, is caused by
a problem with the gene that makes a protein
called dystrophin. This protein helps muscle
cells keep their shape and strength. Without it,
muscles break down and a person gradually
becomes weaker.
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How Is MD Treated?
There's currently no cure for any form of
muscular dystrophy. Research into gene therapy
may eventually provide treatment to stop the
progression of some types of muscular dystrophy.
Current treatment is designed to help prevent or
reduce deformities in the joints and the spine
and to allow people with MD to remain mobile as
long as possible. Treatments may include various
types of physical therapy, medications,
assistive devices and surgery.
MedicationsDoctors prescribe medications to
treat some forms of MD Myotonic dystrophy.
Medications that may be used to help manage the
muscle spasms, stiffness and weakness associated
with this condition include mexiletine,
phenytoin, baclofen, dantrolene and
carbamazepine. Duchenne's muscular dystrophy. The
anti-inflammatory corticosteroid medication
prednisone may help improve muscle strength and
delay the progression of Duchenne's MD.