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Kofi
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 Posted: Sat Oct 04, 2008 5:29 am Post subject: Minocycline corrects Fragile X nerve defects caused by exces |
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http://www.eurekalert.org/pub_releases/2008-10/uoc--urp100308.php
Public release date: 3-Oct-2008
UCR researchers propose minocycline as a promising drug for patients
with Fragile X syndrome
Study leader Iryna Ethell awarded FRAXA Breakthrough Award for 2008
------------------------------------------------------------------------
------------------------------------------------------------------------
First row (left to right): Iryna Ethell, Tina Bilousova; second row (L
to R): Jennifer Aye, Douglas Ethell, Lorraine Dansie, Jonathan Charles
(Michelle Ngo, not shown). Iryna Ethell is holding...
Click here for more information.
------------------------------------------------------------------------
RIVERSIDE, Calif. A UC Riverside-led team of biomedical scientists has
found that a readily available drug called minocycline, used widely to
treat acne and skin infections, can be used to treat Fragile X syndrome,
the most common inherited cause of mental impairment and the most common
cause of autism.
The study>s findings have already impacted future therapies, with the
approval of a new clinical trial in Toronto, Canada, that will test
minocycline in patients with Fragile X.
Neurons in the brain communicate with each other at specialized contact
sites called synapses, with many of these synapses occurring on small
mushroom-shaped structures called dendritic spines.
During early development dendritic spines have immature finger-like
shapes. But learning stabilizes the synapses and dendritic spines take
on a mature mushroom shape, which make them more efficient.
The brains of patients with Fragile X syndrome have an overabundance of
immature dendritic spines.
In their report, the researchers, led by Iryna Ethell and Douglas
Ethell, faculty members in UCR>s Division of Biomedical Sciences,
describe how dendritic spine development in mice with Fragile X is
delayed by enzymes called matrix metalloproteinases (MMPs), which are
involved in normal brain development and physiological processes. They
report that high levels of certain MMPs keep the synapses immature and
inefficient.
But minocycline, they found, reduces these MMP levels in the mice,
allowing the synapses to mature and make more efficient contacts between
neurons in the brain. The outcome: corrected brain abnormalities in
dendritic spines, reduced anxiety and improved cognitive function.
Study results appear online, ahead of print, in the Journal of Medical
Genetics.
In their experiments, the Ethells found that young Fragile X mice
treated with minocycline showed an increase of dendritic spine
maturation in the hippocampus, a brain area that is critical for
learning and memory. Besides less anxiety, minocycline-treated mice
showed better exploration skills as compared to untreated mice.
The Ethells are enthusiastic about how their discovery already is
leading to a clinical trial.
"Clinical studies often quickly follow such basic science because once
there is a solid understanding of how problems arise, it is much easier
to come up with solutions," said Iryna Ethell, an associate professor of
biomedical sciences.
The study was funded by a grant from the FRAXA Research Foundation.
FRAXA was founded in 1994 by three parents of children with Fragile X to
support scientific research aimed at finding a treatment and a cure for
Fragile X.
Dr. Michael Tranfaglia, FRAXA>s chief scientific officer, said of the
UCR researchers, "This group has done something unique and incredibly
valuable: They have identified an off-the-shelf treatment for Fragile X
through their basic research. By bringing their unique perspective to
Fragile X research, they have helped us to understand why neurons are
malformed in this disorder, and more importantly, how we can treat it.
"We were so impressed with their work that we just awarded Dr. Iryna
Ethell the FRAXA Breakthrough Award for 2008. This is easily the most
important scientific breakthrough in the Fragile X field in many years."
According to Dr. Carl Paribello, president of Fragile X Research
Foundation of Canada and the director of the clinical trial (scheduled
for early 2009) at Surrey Place Centre Fragile X Clinic in Toronto,
Canada, the UCR-led study "will go a long way towards dispelling the
idea that mental impairment cannot be treated."
"The work could lead to the first treatment that actually targets the
underlying defect in Fragile X syndrome and not just the symptoms," Dr.
Paribello said.
UCR>s Douglas Ethell, an assistant professor of biomedical sciences,
noted that effective therapies for Fragile X syndrome are few and far
between. "This is a good time for identifying highly effective
therapeutic strategies that might work in Fragile X patients," he said.
"We are excited that our research has the potential to affect many
lives."
Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and
ethnic groups. About 1 in 259 women carry Fragile X and could pass it to
their children. About 1 in 800 men carry Fragile X; their daughters will
also be carriers.
Minocycline belongs to a group of antibiotics that has been used in
people for more than fifty years to treat Lyme disease, acne, and other
skin infections.
Minocycline may have beneficial effects in other disorders where
higher-than-normal brain levels of MMP-9 are found. It is currently
under study for treating rheumatoid arthritis, multiple sclerosis (MS),
Parkinson>s disease, and several other neurodegenerative conditions.
"In the future, new compounds that more specifically target MMP-9 can be
developed and tested," Douglas Ethell said.
Next in their research, the Ethells and their colleagues plan to refine
the therapeutic strategy in Fragile X mice to determine the optimal age,
if any, to administer minocycline. They will also explore other MMP
inhibitors that may be more effective than minocycline.
"We will investigate whether a combination of MMP inhibitors with other
drugs, such as fenobam, can help mature the synapses in Fragile X mice,"
Iryna Ethell said.
###
The Ethells were joined in the research by UCR>s Tina Bilousova,
Lorraine Dansie, Michelle Ngo, Jennifer Aye, Jonathan R. Charles, all of
whom are in the Division of Biomedical Sciences and Neuroscience Program.
UCR>s Office of Technology Commercialization has applied for a patent on
the discovery by the Ethells and their collaborators, with an interest
in finding partners to accelerate development of treatments for Fragile
X syndrome and other forms of mental retardation and autism.
The University of California, Riverside is a doctoral research
university, a living laboratory for groundbreaking exploration of issues
critical to Inland Southern California, the state and communities around
the world. Reflecting California>s diverse culture, UCR>s enrollment of
about 17,000 is expected to grow to 21,000 students by 2020. The campus
is planning a medical school and has reached the heart of the Coachella
Valley by way of the UCR Palm Desert Graduate Center. The campus has an
annual statewide economic impact of more than $1 billion. To learn more,
visit www.ucr.edu or call (951) UCR-NEWS.
------------------------------------------------------------------------
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Ernie Primeau
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| Posted: Sun Oct 05, 2008 3:52 am Post subject: Re: Minocycline corrects Fragile X nerve defects caused by e |
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Just as I suspected. Ernie
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John Hasenkam
Guest
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| Posted: Sun Oct 05, 2008 7:24 am Post subject: Re: Minocycline corrects Fragile X nerve defects caused by e |
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Hey Kofi,
It inhibits nitric oxide synthesis, possibly via inhibition of p38. It won>t
cure Fragile X or any other condition, it lower inflammation, that>s all.
John.
"Kofi" <kofi@anon.un> wrote in message
news:kofi-EEF993.23063903102008@news.west.earthlink.net...
[quote]http://www.eurekalert.org/pub_releases/2008-10/uoc--urp100308.php
Public release date: 3-Oct-2008
UCR researchers propose minocycline as a promising drug for patients
with Fragile X syndrome
Study leader Iryna Ethell awarded FRAXA Breakthrough Award for 2008
------------------------------------------------------------------------
------------------------------------------------------------------------
First row (left to right): Iryna Ethell, Tina Bilousova; second row (L
to R): Jennifer Aye, Douglas Ethell, Lorraine Dansie, Jonathan Charles
(Michelle Ngo, not shown). Iryna Ethell is holding...
Click here for more information.
------------------------------------------------------------------------
RIVERSIDE, Calif. A UC Riverside-led team of biomedical scientists has
found that a readily available drug called minocycline, used widely to
treat acne and skin infections, can be used to treat Fragile X syndrome,
the most common inherited cause of mental impairment and the most common
cause of autism.
The study>s findings have already impacted future therapies, with the
approval of a new clinical trial in Toronto, Canada, that will test
minocycline in patients with Fragile X.
Neurons in the brain communicate with each other at specialized contact
sites called synapses, with many of these synapses occurring on small
mushroom-shaped structures called dendritic spines.
During early development dendritic spines have immature finger-like
shapes. But learning stabilizes the synapses and dendritic spines take
on a mature mushroom shape, which make them more efficient.
The brains of patients with Fragile X syndrome have an overabundance of
immature dendritic spines.
In their report, the researchers, led by Iryna Ethell and Douglas
Ethell, faculty members in UCR>s Division of Biomedical Sciences,
describe how dendritic spine development in mice with Fragile X is
delayed by enzymes called matrix metalloproteinases (MMPs), which are
involved in normal brain development and physiological processes. They
report that high levels of certain MMPs keep the synapses immature and
inefficient.
But minocycline, they found, reduces these MMP levels in the mice,
allowing the synapses to mature and make more efficient contacts between
neurons in the brain. The outcome: corrected brain abnormalities in
dendritic spines, reduced anxiety and improved cognitive function.
Study results appear online, ahead of print, in the Journal of Medical
Genetics.
In their experiments, the Ethells found that young Fragile X mice
treated with minocycline showed an increase of dendritic spine
maturation in the hippocampus, a brain area that is critical for
learning and memory. Besides less anxiety, minocycline-treated mice
showed better exploration skills as compared to untreated mice.
The Ethells are enthusiastic about how their discovery already is
leading to a clinical trial.
"Clinical studies often quickly follow such basic science because once
there is a solid understanding of how problems arise, it is much easier
to come up with solutions," said Iryna Ethell, an associate professor of
biomedical sciences.
The study was funded by a grant from the FRAXA Research Foundation.
FRAXA was founded in 1994 by three parents of children with Fragile X to
support scientific research aimed at finding a treatment and a cure for
Fragile X.
Dr. Michael Tranfaglia, FRAXA>s chief scientific officer, said of the
UCR researchers, "This group has done something unique and incredibly
valuable: They have identified an off-the-shelf treatment for Fragile X
through their basic research. By bringing their unique perspective to
Fragile X research, they have helped us to understand why neurons are
malformed in this disorder, and more importantly, how we can treat it.
"We were so impressed with their work that we just awarded Dr. Iryna
Ethell the FRAXA Breakthrough Award for 2008. This is easily the most
important scientific breakthrough in the Fragile X field in many years."
According to Dr. Carl Paribello, president of Fragile X Research
Foundation of Canada and the director of the clinical trial (scheduled
for early 2009) at Surrey Place Centre Fragile X Clinic in Toronto,
Canada, the UCR-led study "will go a long way towards dispelling the
idea that mental impairment cannot be treated."
"The work could lead to the first treatment that actually targets the
underlying defect in Fragile X syndrome and not just the symptoms," Dr.
Paribello said.
UCR>s Douglas Ethell, an assistant professor of biomedical sciences,
noted that effective therapies for Fragile X syndrome are few and far
between. "This is a good time for identifying highly effective
therapeutic strategies that might work in Fragile X patients," he said.
"We are excited that our research has the potential to affect many
lives."
Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and
ethnic groups. About 1 in 259 women carry Fragile X and could pass it to
their children. About 1 in 800 men carry Fragile X; their daughters will
also be carriers.
Minocycline belongs to a group of antibiotics that has been used in
people for more than fifty years to treat Lyme disease, acne, and other
skin infections.
Minocycline may have beneficial effects in other disorders where
higher-than-normal brain levels of MMP-9 are found. It is currently
under study for treating rheumatoid arthritis, multiple sclerosis (MS),
Parkinson>s disease, and several other neurodegenerative conditions.
"In the future, new compounds that more specifically target MMP-9 can be
developed and tested," Douglas Ethell said.
Next in their research, the Ethells and their colleagues plan to refine
the therapeutic strategy in Fragile X mice to determine the optimal age,
if any, to administer minocycline. They will also explore other MMP
inhibitors that may be more effective than minocycline.
"We will investigate whether a combination of MMP inhibitors with other
drugs, such as fenobam, can help mature the synapses in Fragile X mice,"
Iryna Ethell said.
###
The Ethells were joined in the research by UCR>s Tina Bilousova,
Lorraine Dansie, Michelle Ngo, Jennifer Aye, Jonathan R. Charles, all of
whom are in the Division of Biomedical Sciences and Neuroscience Program.
UCR>s Office of Technology Commercialization has applied for a patent on
the discovery by the Ethells and their collaborators, with an interest
in finding partners to accelerate development of treatments for Fragile
X syndrome and other forms of mental retardation and autism.
The University of California, Riverside is a doctoral research
university, a living laboratory for groundbreaking exploration of issues
critical to Inland Southern California, the state and communities around
the world. Reflecting California>s diverse culture, UCR>s enrollment of
about 17,000 is expected to grow to 21,000 students by 2020. The campus
is planning a medical school and has reached the heart of the Coachella
Valley by way of the UCR Palm Desert Graduate Center. The campus has an
annual statewide economic impact of more than $1 billion. To learn more,
visit www.ucr.edu or call (951) UCR-NEWS.
------------------------------------------------------------------------
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