The Dino-Aspie Ex-Café (for Those 40+... or feeling creaky)

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okaaayyy, then. it's time to go do the laundry.....

I love that last cartoon!

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that was priceless!

Merle

reading and lurking

Minocycline As A Promising Drug For Patients With Fragile X Syndrome Proposed By UCR Researchers
04 Oct 2008

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.

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Article adapted by Medical News Today from original press release.
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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 http://www.ucr.edu/.

Source: Iqbal Pittalwala
University of California - Riverside

Article URL: http://www.medicalnewstoday.com/articles/124215.php

Main News Category: Biology / Biochemistry

Also Appears In: Genetics, Autism, Clinical Trials / Drug Trials,

Hello to all!
Love your artwork Lemon! Good work raising Spike Nan! Good stuff all! I hope that you are all well. I'll be basically living at work until next January - two of our pharmacists are out with knee surgeries, and one is out with a shoulder surgery. (Who knew that pharmacy could be so physical? )

I'll try to check in from time to time.

Take care!
Chuck

but, but Chuck. . .the water rivulets down the shower wall. . .the opera aria. . .??! !

what does blue bear say about you working all the time??

merle

Thanks for reminding me Merle! Perhaps it is time to remember "not just another day! ..."
Blue bear is worn out, but never complains. I can always rely his antics providing a good laugh when things get tough.

Just as the winter season is cranking up, and our script count is beginning its annual climb, our aging shortage-hindered pharmacists are breaking down. And due to the recently signed "bail-out bill", our pharmacy technician workforce hours were immediately cut by management-powers-that-be 30% - with the possibility of further workforce reductions (i.e., let half of them go). Oy.

So hang tough Merle, and everyone else. (good to hear from you, sweetie! ) Good times can exist in the mind even if they can't on the outside. And as the toaists teach: "down cycles" are always followed by "up cycles". Even in the worst of times you can smile - knowing that good times are certainly ahead.

Then again, "Life's a b***h, and then you die." comes to mind as well.

Lau probably has an appropriate twisted aphorism in his collections.

Ah, well. Work beckons, and I must respond - if only to show that when the going gets tough, Aspies prevail.


Luv yas!
Chuck

Lurking and smiling...

.....When the going gets tough Aspies prevail! (Chuck) ....

A curious article, Chuck. Since when has Fragile X syndrome been "the most common cause of autism"?

I didn't even think it was classed as related, these days.

While the treatment sounds pretty promising, I'd suspect it was rather early days.

Naturally, as Fragile X is identified as genetic disorder, this treatment, which addresses a known physical expression of that, is in no way a cure of Fragile X itself.

===========

PS. Ah... that's interesting. This report of a development at UCR, seems to borrow bits out of this earlier one, supposedly reporting the same sort of research, but at MIT:
http://www.eurekalert.org/pub_releases/ ... 062507.php

I think I'm confused.

In date order, from the horses' moutheses:

http://web.mit.edu/newsoffice/2007/fragilex-0625.html
http://web.mit.edu/newsoffice/2007/fragilex-1219.html
http://newsroom.ucr.edu/cgi-bin/display.cgi?id=1933

I can't remember on which day I went to this:

There aren't many eight and a half hour long plays.

Good points Lau! Seems treating the physical expression is the best that can be done at present. Actual correction of defective gene(s) is still in the experimental stages - that field is in its relative infancy as yet. Science is accelerating at such a rate we may see corrections in certain disorders in our lifetime! (who will regulate this field? ...and should we? ...and how far should we go in gene alteration? ...and how big a bag of popcorn did it take to make it through an eight and a half hour long play?!?)
Another problem (although, by comparison to Fragile X , is merely cosmetic): minocycline is not supposed to be administered to children under the age of 8 years old, as it causes mottled brown/black discoloration of the permanent teeth. I suppose this could be cosmetically corrected, but I have seen how it causes embarrassment to adults whose teeth have been permanently discolored by tetracyclines.

hey, now, you can't take popcorn into a play. It is just not done. You may belt back a couple of short ones during the interval, or have a couple of cookies for sustanance (and for an 8 hour play, those little crustless sandwiches, perhaps) but popcorn at a live play? bad form!

Merle

There was a dinner break. I seem to recall running, to get to "The George [Inn]" at the end. End of play 10:30pm, closing time 11pm. I don't think we made it.
http://www.revver.com/video/616611/the- ... london-uk/

Maybe we didn't even try to get there... it's further than I thought!