Open-Label Sulforaphane Trial in FMR1 Premutation Carriers with Fragile-X-Associated Tremor and Ataxia Syndrome (FXTAS)
Ellery Santos,
Courtney Clark,
Hazel Maridith B. Biag,
Si Jie Tang,
Kyoungmi Kim,
Matthew D. Ponzini,
Andrea Schneider,
Cecilia Giulivi,
Federica Alice Maria Montanaro,
Jesse Tran-Emilia Gipe,
Jacquelyn Dayton,
Jamie L. Randol,
Pamela J. Yao,
Apostolos Manolopoulos,
Dimitrios Kapogiannis,
Ye Hyun Hwang,
Paul Hagerman,
Randi Hagerman,
Flora Tassone
Affiliations
Ellery Santos
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Courtney Clark
Department of Pediatrics, School of Medicine, University of California, Davis, CA 95817, USA
Hazel Maridith B. Biag
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Si Jie Tang
Department of Pediatrics, School of Medicine, University of California, Davis, CA 95817, USA
Kyoungmi Kim
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Matthew D. Ponzini
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Andrea Schneider
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Cecilia Giulivi
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Federica Alice Maria Montanaro
Child and Adolescent Neuropsychiatry Unit, Department of Neuroscience, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy
Jesse Tran-Emilia Gipe
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
Jacquelyn Dayton
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
Jamie L. Randol
Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA 95616, USA
Pamela J. Yao
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 212241, USA
Apostolos Manolopoulos
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 212241, USA
Dimitrios Kapogiannis
Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 212241, USA
Ye Hyun Hwang
Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, CA 95616, USA
Paul Hagerman
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Randi Hagerman
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Flora Tassone
Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California Davis Health, Sacramento, CA 95817, USA
Fragile X (FMR1) premutation is a common mutation that affects about 1 in 200 females and 1 in 450 males and can lead to the development of fragile-X-associated tremor/ataxia syndrome (FXTAS). Although there is no targeted, proven treatment for FXTAS, research suggests that sulforaphane, an antioxidant present in cruciferous vegetables, can enhance mitochondrial function and maintain redox balance in the dermal fibroblasts of individuals with FXTAS, potentially leading to improved cognitive function. In a 24-week open-label trial involving 15 adults aged 60–88 with FXTAS, 11 participants successfully completed the study, demonstrating the safety and tolerability of sulforaphane. Clinical outcomes and biomarkers were measured to elucidate the effects of sulforaphane. While there were nominal improvements in multiple clinical measures, they were not significantly different after correction for multiple comparisons. PBMC energetic measures showed that the level of citrate synthase was higher after sulforaphane treatment, resulting in lower ATP production. The ratio of complex I to complex II showed positive correlations with the MoCA and BDS scores. Several mitochondrial biomarkers showed increased activity and quantity and were correlated with clinical improvements.
