Minocycline Promising for Fragile X Syndrome - autism, MMP-9

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Minocycline Promising for Fragile X Syndrome - autism, MMP-9

Postby Longing4Cheese » Sat Oct 11, 2008 11:48 pm

Forgive me if this is already covered -- I did search for "autism" in the Antibiotics forum and got zero results. So, this may be very interesting news...

UCR Researchers Propose Minocycline as a Promising Drug for Patients with Fragile X Syndrome

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.

Full article and links:

http://info.ucr.edu/cgi-bin/display.cgi?id=1933

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Postby MacKintosh » Sun Oct 12, 2008 4:30 pm

This is always of interest to me, as one of my dearest friends has an autistic son.

If you want more, stop by the CPn Help.org website. There have been several conversations on abx and autism there. This website disables links to that site, so just put 'org' behind the website name.
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Postby SarahLonglands » Wed Oct 15, 2008 9:39 am

Ah, but to be fair Mac, if I make a link here: http://www.CPn Help.org, it might look funny, but if you click on it, it will take you straight to the site.

This info is very interesting, though.......Sarah
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
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Postby MacKintosh » Wed Oct 15, 2008 10:34 am

Agreed, Sarah; IF you make a link, it doesn't 'read' properly, but it will work. I added that particular comment because, when I submitted my post and typed in just the name of the website, 'org' was automatically eliminated from my post.
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Postby SarahLonglands » Wed Oct 15, 2008 10:55 am

Blame Bromley! Sarah :wink:
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
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Postby MacKintosh » Wed Oct 15, 2008 11:07 am

AH! He-who-must-not-be-named! :wink:

Back on topic, I passed this paper on to my friend with the autistic son. He said it's pretty specific to autism caused by mothers who drank heavily while the child was in utero, but he is intrigued by the idea of abx for autism. Let's see if he can engage his ex-wife in pursuing this for their son...
The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi
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Postby SarahLonglands » Thu Oct 16, 2008 11:14 am

Hang on a minute, I didn't know that autism could be caused by mothers drinking heavily when pregnant, so aren't they just assuming, in the same way that a certain doctor in this country caused a measles epidemic by making parents frightened of the MMR jab a few years ago because that was given at the age when autism first develops.

Keep on intriguing your friend...............Sarah
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
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Postby notasperfectasyou » Thu Oct 16, 2008 12:11 pm

I miss the panda
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Postby MacKintosh » Thu Oct 16, 2008 10:53 pm

I know, Sarah, I know. It seems the autism community is saddled with the same old wive's tales and innuendo we MSers have to contend with. He's going to broach it to his ex. He's actually planning to do abx himself, for a number of medical issues of his own.
The difference between what we do and what we are capable of doing would suffice to solve most of the world’s problems. Mohandas Gandhi
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Postby SarahLonglands » Fri Oct 17, 2008 5:48 am

Mac, its sometimes hard to find anything that isn't riddled with old wives tales and innuendo but good that your friend is going to broach the subject to his ex and also that h is going to sort out his own medical issues.

By the way, what is cpi? :?
An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.
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