Minocycline show benefits in children with inherited cause of intellectual disability and autism

The antibiotic drug minocycline yields “modest” but meaningful improvements in functioning and mood for children with fragile X syndrome (FXS), reports a study in the April Journal of Developmental & Behavioral Pediatrics, the official journal of the Society for Developmental and Behavioral Pediatrics. The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.

Three months of treatment with minocycline in children with FXS resulted in greater overall improvement than placebo treatment, according to the study by Dr Mary Jacena S. Leigh of University of California Davis Medical Center, Sacramento, and colleagues. They write, “This study is important because minocycline is a targeted treatment for FXS that is currently available by prescription.”

‘Global Improvement’ with Minocycline in Kids with FXS

Fragile X syndrome, which causes intellectual disability and behavioral and learning problems, affects about 1 in 4,000 males in the United States. It also occurs in females, but typically causes less severe impairment. Caused by mutations of a gene called FMR1, FXS is the most common cause of inherited intellectual disability and the most common genetic cause of autism and autism-spectrum disorders.

In the study, 66 children with FXS were randomly assigned to three months of treatment with minocycline or inactive placebo. After three months, they were switched to the other treatment. Parents and doctors were unaware of which treatment the child was receiving until the child completed the study.

Fifty-five patients completed the study. The children had small but significant improvements in certain areas during treatment with minocycline, compared to placebo. In particular, they scored better on the Clinical Global Impression Scale, where doctors rated their overall impression of the patients’ status. Average scores on the 7-point rating scale were 2.5 points for children taking minocycline versus 3 points for those taking placebo: a 0.5-point improvement with minocycline in comparison to placebo.

Children taking minocycline also had greater improvement in anxiety and mood-related behaviors, as rated by parents. Other outcomes were not significantly better with minocycline, including behavior problems and verbal functioning.

Side effects were generally similar between groups, with no serious adverse effects. Minocycline may cause some discoloration of the teeth- a known side effect of minocycline and related antibiotics, which was seen in both treatment arms.

Minocycline Is Only Available ‘Targeted Treatment’ for FXS

Minocycline is an older antibiotic, perhaps most commonly used for treatment of severe acne. Animal experiments and initial studies in humans have suggested that it might have beneficial effects in the treatment of FXS. Minocycline has also been studied as a potential “neuroprotective” treatment in other conditions, such as multiple sclerosis.

This preliminary clinical trial shows small but significant benefits of minocycline in children with FXS. Other treatments for FXS are being investigated, including a new class of drugs called mGluR5 inhibitors. However, minocycline is the only targeted FXS treatment that is currently available by prescription. Because of its long history of use, the side effects and safety characteristics of minocycline are well known.

More research will be needed to determine how minocycline exerts its beneficial effects in FXS, and to clarify the most effective dose and length of treatment. “Further studies including long term follow up on individuals treated with minocycline are warranted with a careful assessment of side effects and benefits,” Dr Leigh and colleagues conclude.