Side Effects of Minocycline Treatment in Patients With Fragile X Syndrome and Exploration of Outcome Measures

Abstract

Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received minocycline for at least 2 weeks and found that the most common reported side effect is gastrointestinal difficulty, including loss of appetite. The families reported an improvement in language and behavioral areas. Outcome measures in the design of future randomized clinical trials should include both behavioral and language measures. As with any other treatments, we emphasize that randomized clinical trials are needed to determine the efficacy of minocycline in fragile X syndrome.

Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics

“…In FXS mice, upon minocycline treatment, synaptic maturation was rescued, and mice demonstrated improvements in anxiety and in a cognitive task (125). This work stimulated a survey study of families whose children were treated with minocycline, and 70% noted an improvement in behavior or language (126). In addition, an open trial in adolescent and adult males with FXS demonstrated efficacy in all of the outcome measures (127).…”

Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us

“…Treatment of dFmr1 null animals with minocycline restored the abnormal synaptic morphology observed in three different neuronal areas: the neuromuscular junction (NMJ), the clock neurons, and the Kenyon cells of MBs (Siller and Broadie 2011). Finally, minocycline administration in patients with FXS was shown to improve attention deficits, language use, and communication skills (Paribello et al 2010;Utari et al 2010;Leigh et al 2013).…”

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

“…All aspects of the phenotype are more evident in males than females, as females express FMRP from the normal X chromosome, the amount of which depends on X inactivation ratios. Physical features and associated medical problems Hagerman et al, 2009) are variably present and include: macroorchidism (present in most adult males), prominent ears, macrocephaly, long face, high arched palate, hyperextensible joints, soft skin, recurrent otitis media and sinusitis, gastroesophageal reflux, strabismus and farsightedness (Maino et al, 1991), hyperphagia and obesity Utari et al, 2010), mitral valve prolapse and valvular insufficiency (particularly in adults), pes planus (flat feet), joint dislocations, scoliosis, disrupted sleep patterns (Kronk et al, 2010), and obstructive sleep apnea. Seizures occur in B15% of males and 6-8% of females with FXS, and most commonly are partial complex (Musumeci et al, 1999;Berry-Kravis, 2002;Berry-Kravis et al, 2010), have onset between age 4 and 10 years, and resolve during childhood, although presence of seizures appears to be an indicator of an increased risk for autism in FXS (Berry-Kravis, 2002;Berry-Kravis et al, 2010).…”

“…The high risk of irreversible yellow/brown discoloration of the permanent teeth in children aged o12 years exposed to minocycline, coupled with the idea that targeted treatments might work better if applied at younger ages, has made it crucial to understand the true margin of benefit for this treatment. The other side effects that can be seen at any age include GI symptoms such as vomiting and/or diarrhea (Utari et al, 2010), drug-induced lupus, and pseudotumor cerebri.…”