Navigation Links
UCR researchers propose minocycline as a promising drug for patients with Fragile X syndrome
Date:10/3/2008

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.


'/>"/>

Contact: Iqbal Pittalwala
iqbal@ucr.edu
951-827-6050
University of California - Riverside
Source:Eurekalert  

Related biology news :

1. Childrens National researchers develop novel anti-tumor vaccine
2. Case Western Reserve University researchers track Chernobyl fallout
3. Researchers develop new self-training gene prediction program for fungi
4. UI researchers find potentially toxic substance present in Chicago air
5. Researchers study how pistachios may improve heart health
6. Researchers discover that growing up too fast may mean dying young in honey bees
7. Researchers study acoustic communication in deep-sea fish
8. Researchers note differences between people and animals on calorie restriction
9. Researchers find an essential gene for forming ears of corn
10. Researchers find animal with ability to survive climate change
11. NC State researchers get to root of parasite genome
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UCR researchers propose minocycline as a promising drug for patients with Fragile X syndrome
(Date:6/23/2017)... ITHACA, N.Y. , June 23, 2017 /PRNewswire/ ... leader in dairy research, today announced a new collaboration ... reduce the chances that the global milk supply is ... dairy project, Cornell University has become the newest academic ... Supply Chain, a food safety initiative that includes IBM ...
(Date:5/16/2017)... 16, 2017   Bridge Patient Portal , ... MD EMR Systems , an electronic medical ... GE, have established a partnership to build an ... the GE Centricity™ products, including Centricity Practice Solution ... These new integrations will allow healthcare delivery ...
(Date:4/18/2017)... a global expert in SoC-based imaging and computing solutions, has developed ... the company,s hybrid codec technology. A demonstration utilizing TeraFaces ® , ... showcased during the upcoming Medtec Japan at Tokyo Big Sight April ... Vegas Convention Center April 24-27. ... Click here for an image of the M820 ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... 2017 , ... A new study published in Fertility and ... in vitro fertilization (IVF) transfer cycles. The multi-center matched cohort study ... comparing the results from the fresh and frozen transfer cohorts, the authors of ...
(Date:10/10/2017)... CA (PRWEB) , ... October ... ... a development-stage cancer-focused pharmaceutical company advancing targeted antibody-drug conjugate (ADC) therapeutics, today ... of targeted HPLN (Hybrid Polymerized Liposomal Nanoparticle), a technology developed in collaboration ...
(Date:10/10/2017)... International research firm Parks Associates announced today that ... TMA 2017 Annual Meeting , October 11 in Scottsdale, ... security market and how smart safety and security products impact the competitive ... Parks Associates: Smart Home Devices: Main ... "The residential security market has experienced continued ...
(Date:10/10/2017)... ... 2017 , ... The Pittcon Program Committee is pleased to ... who have made outstanding contributions to analytical chemistry and applied spectroscopy. Each award ... conference and exposition for laboratory science, which will be held February 26-March 1, ...
Breaking Biology Technology: