Results Suggest it can Improve Challenging Behaviors
A FRAXA-funded study of minocyline in mice, by the Ethell lab at UC-Riverside, discovered that a drug called minocycline can reverse structural abnormalities seen in the brain cells of Fragile X mice.
With a $40,000 grant from FRAXA, Dr. Carlo Paribello and his team at the Surrey Place Centre Fragile X clinic in Toronto, Ontario, ran 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 took minocycline for two months. Dr. Paribello is himself the father of two boys with Fragile X.
Patients received either 100 mg or 200 mg of minocycline daily, and their behaviors were evaluated prior to treatment and again 8 weeks after daily minocycline. Behavioral scores showed striking improvement and the drug was generally well tolerated. The most significant side effect noted was, in blood tests, an asymptomatic seroconversion to a positive ANA in two people. This is a nonspecific marker of immunoinflammatory connective tissue diseases, so physicians who prescribe minocycline should be aware of its risk for inducing potentially serious autoimmune phenomena.
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.
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