The study, “A randomized placebo controlled clinical trial to evaluate the efficacy and safety of minocycline in patients with Angelman syndrome (A-MANECE study),” was published in the Orphanet Journal of Rare Diseases.
Angelman syndrome is a rare neurological genetic condition. It is characterized by developmental delays, learning disabilities, severe speech impairment, and lack of muscle coordination. Currently, there is no cure and most treatments, including medication and physical/behavioral therapies, focus on keeping symptoms at bay and improving patients’ quality of life.
Minocycline — a type of tetracycline antibiotic used to treat bacterial infections — has been shown to have antioxidant, anti-inflammatory, anti-cell death and neuroprotective properties in neurological disease mouse models.
These promising preclinical findings led scientists to believe that minocycline might become a treatment option for several neurological disorders, including fragile X syndrome, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s, Parkinson’s and Angelman syndrome.
Although previous single-arm clinical trials suggested minocycline was beneficial in the treatment of Angelman syndrome, its effectiveness had never been evaluated in a controlled clinical trial.
Researchers designed a controlled Phase 2 trial to assess the drug’s action on developmental effects in patients with Angelman syndrome, along with its safety and tolerability.
The randomized, double-blind, placebo-controlled, crossover A-MANECE study (NCT02056665, EudraCT 2013-002154-67) recruited 32 people diagnosed with Angelman syndrome between the ages of 6 and 30 from January 2014 to September 2014.
Participants were randomly given either minocycline (with daily doses ranging from 100mg to 200mg, depending on patients’ weight) or a placebo for eight weeks. After the initial treatment period, 22 patients switched to the other treatment (either minocycline or placebo) and 10 received minocycline for up to 16 weeks. After week 16, all patients underwent an eight-week “wash-out” period — a time when a participant is taken off a study compound to eliminate the effects of the treatment.
There were no significant differences in the development index, as determined by the Merrill-Palmer Revised Scale, after minocycline treatment compared to the placebo. This scale assesses cognitive, social-emotional, self-help, and fine and gross motor development in infants and children. Moreover, the extended treatment of 16 weeks also failed to improve patient outcomes.
The minocycline was considered safe and well-tolerated by the participants, with no significant side effects or serious adverse events during the study attributed to its administration.
“Treatment with minocycline appears safe and well-tolerated; even if it cannot be completely ruled out that longer trials might be required for a potential minocycline effect to be expressed, available results and lack of knowledge on the actual mechanism of action do not support this hypothesis,” the authors wrote.
These findings suggest that minocycline does not provide significant clinical benefits that should warrant its recommendation as a valid treatment for Angelman syndrome.
“In this first randomized placebo-controlled study conducted in patients with [Angelman syndrome], minocycline failed to demonstrate any benefits in the relevant neurological areas affected in AS. These results do not warrant the use of minocycline in AS,” they concluded.