Pilot Trial of Minocycline in Fragile X

FRAXA Awards:

$40,000 in 2008

Grant to Carlos Paribello, PhD — Fragile X Research Foundation of Canada

This trial is based on results of a FRAXA-funded study of minocyline in mice, by the Ethell lab at UC-Riverside.

Researchers funded by FRAXA have discovered that a drug called minocycline can reverse structural abnormalities seen in the brain cells of Fragile X mice. Minocycline belongs to a group of antibiotics called synthetic tetracyclines, and it has been used in people for more than fifty years to treat Lyme disease, acne, and other skin infections.

With a $40,000 grant from FRAXA, Dr. Carlo Paribello and his team at the Surrey Place Centre Fragile X clinic in Toronto, Ontario, are running an open label trial to see if minocycline can improve learning and reduce anxiety and behavioral problems in people with Fragile X. Twenty participants between the ages of 13 and 35 years take minocycline for two months. If the medication is helpful, they have the option of continuing it for a year.

Dr. Paribello is president and co-founder of the Fragile X Research Foundation of Canada, a long-time partner with FRAXA in our work to find effective treatments and a cure for Fragile X. Dr. Paribello is also the father of two boys with Fragile X.

It has been known for some time that minocycline inhibits a protein called matrix metalloproteinase-9, (MMP-9). MMPs are involved in normal development and physiological processes such as wound repair and tissue remodeling, as well as in disease processes such as arthritis. FRAXA-funded studies have shown that MMP-9 levels are abnormally high in the brains of Fragile X mice – probably as a result of excessive mGluR5 signaling. In the mouse studies, minocycline reduced MMP-9 levels in the brain, corrected brain abnormalities in dendritic spines, and reduced anxiety, all while improving cognitive function. Excessive MMP-9 activity may also contribute to the lax connective tissue phenotype often seen in children who have Fragile X.

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.

Minocycline is generally well-tolerated with a long record of use in humans, although it is not recommended for patients under 8 years of age due a risk of permanent tooth discoloration/staining. Medically serious adverse effects occur in about 1 in 5-10,000 patients. While many people are concerned about the development of resistant strains of bacteria during chronic antibiotic administration, this is not a major concern with this drug. Most bacteria which can acquire tetracycline (or minocycline) resistance have already done so; minocycline is currently only used to treat infections by bacteria which are incapable of acquiring tetracycline resistance.

Thus, a medication which had been relegated to the rather lowly status of chronic treatment for acne has been found to have potentially important new uses unrelated to its antibiotic activity. This trial will be the beginning of a process to assess its value in the treatment of Fragile X.

Access the paper here: Open-label add-on treatment trial of minocycline in Fragile X syndrome

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