A
team of researchers from the US, UK and China, has developed an impressive new
technology that will enable the mass screening of drug compounds to identify
those that may promote repair of the myelin sheath that is damaged in the brain
and spinal cords of people with MS.
team of researchers from the US, UK and China, has developed an impressive new
technology that will enable the mass screening of drug compounds to identify
those that may promote repair of the myelin sheath that is damaged in the brain
and spinal cords of people with MS.
The
research was published in the top medical journal Nature Medicine last week. The abstract
describes the development of an array of nanofibres that can be produced in
laboratory cell culture dishes. The fibres provide a scaffolding that mimics
the long thin nerve fibres (axons) in the brain and spinal cord, allowing
researchers to monitor the growth of myelin-producing cells in the dish and
their ability to wrap the scaffolding in myelin.
research was published in the top medical journal Nature Medicine last week. The abstract
describes the development of an array of nanofibres that can be produced in
laboratory cell culture dishes. The fibres provide a scaffolding that mimics
the long thin nerve fibres (axons) in the brain and spinal cord, allowing
researchers to monitor the growth of myelin-producing cells in the dish and
their ability to wrap the scaffolding in myelin.
Loss
of myelin during the inflammatory attacks of MS leads to disruption of the
conduction of messages along nerves, causing the symptoms of MS such as
weakness, vision loss and pain. During periods of remission in MS, myelin can
be repaired and symptoms improve, however, over time myelin repair fails and
exposed axons become irreversibly damaged leading to permanent disability.
Understanding how myelin repair (remyelination) may be encouraged is therefore
a key target of MS research.
of myelin during the inflammatory attacks of MS leads to disruption of the
conduction of messages along nerves, causing the symptoms of MS such as
weakness, vision loss and pain. During periods of remission in MS, myelin can
be repaired and symptoms improve, however, over time myelin repair fails and
exposed axons become irreversibly damaged leading to permanent disability.
Understanding how myelin repair (remyelination) may be encouraged is therefore
a key target of MS research.
The
process of remyelination is dependent on several steps including an increase in
number of myelin-producing oligodendrocyte precursor cells, the movement of the
cells to the site of damage, and finally the proper wrapping of a new
functional myelin sheath around nerve axons.
process of remyelination is dependent on several steps including an increase in
number of myelin-producing oligodendrocyte precursor cells, the movement of the
cells to the site of damage, and finally the proper wrapping of a new
functional myelin sheath around nerve axons.
The
technology developed by the researchers is an array of silicon ‘micro-pillars’
contained within a typical cell culture dish, known as a 96-well plate. 96-well
plates are commonly used in large automated laboratory assays in which a
separate ‘experiment’ can be performed in each of the 96 miniature ‘test-tubes’
on the plate.
technology developed by the researchers is an array of silicon ‘micro-pillars’
contained within a typical cell culture dish, known as a 96-well plate. 96-well
plates are commonly used in large automated laboratory assays in which a
separate ‘experiment’ can be performed in each of the 96 miniature ‘test-tubes’
on the plate.
The
structure of the silicon micro-pillars mimics the structure of nerve axons,
allowing oligodendrocytes growing in the dish to move to the pillars and wrap
myelin layers around the pillar, just as they would with an axon in the brain.
The researchers were able to use specialised microscope techniques to observe
and quantify the efficiency of myelin wrapping around the micro-pillars.
structure of the silicon micro-pillars mimics the structure of nerve axons,
allowing oligodendrocytes growing in the dish to move to the pillars and wrap
myelin layers around the pillar, just as they would with an axon in the brain.
The researchers were able to use specialised microscope techniques to observe
and quantify the efficiency of myelin wrapping around the micro-pillars.
Using
this technique the researchers screened a library of 1000 potential drug molecules
and discovered a group of eight molecules that increased the amount of myelin
wrapping. The molecules are all known to act via a similar mechanism in
blocking a particular receptor molecule found on neurons, known as muscarinic
receptors.
this technique the researchers screened a library of 1000 potential drug molecules
and discovered a group of eight molecules that increased the amount of myelin
wrapping. The molecules are all known to act via a similar mechanism in
blocking a particular receptor molecule found on neurons, known as muscarinic
receptors.
Of
particular interest, two of these molecules, Clemastine and benzatropine, have
previously been approved by the US Federal Drugs Administration (FDA) for other
conditions and are also known to cross the blood brain barrier – an essential
prerequisite for a drug intended to repair damage within the brain.
particular interest, two of these molecules, Clemastine and benzatropine, have
previously been approved by the US Federal Drugs Administration (FDA) for other
conditions and are also known to cross the blood brain barrier – an essential
prerequisite for a drug intended to repair damage within the brain.
The
researchers went on to show that Clemastine was able to increase remyelination
of axons in a mouse model of myelin damage, and may be worth pursuing in
pre-clinical and clinical studies for MS.
researchers went on to show that Clemastine was able to increase remyelination
of axons in a mouse model of myelin damage, and may be worth pursuing in
pre-clinical and clinical studies for MS.
The
researchers say that they are confident that expanding the use of the
technology to screen larger chemical libraries, including more FDA-approved
compounds and new molecules, will result in the identification and development
of new therapies for repair in multiple sclerosis.
researchers say that they are confident that expanding the use of the
technology to screen larger chemical libraries, including more FDA-approved
compounds and new molecules, will result in the identification and development
of new therapies for repair in multiple sclerosis.
MS Research Australia is funding a number of
studies targeting remyelination in MS including Dr Simon
Murray and Dr
Stan Mitew both at the University of Melbourne.
studies targeting remyelination in MS including Dr Simon
Murray and Dr
Stan Mitew both at the University of Melbourne.
Source : MS Research Australia
~~~~~~~~~~~~~~~~~~~~
Keep CURRENT and up to date, with MS News and Information
Sign-up for emails
.
WATCH OUR MS EDUCATIONAL VIDEOS by Topic,
found here: www.youtube.com/msviewsandnews
.
Visit our MS Learning Channel on YouTube: http://www.youtube.com/msviewsandnews