Voice of People with Fragile X Syndrome and Their Families: Reports from a Survey on Treatment Priorities

Weber, Jayne Dixon; Smith, Elizabeth G.; Berry‐Kravis, Elizabeth; Cadavid, Diego; Hessl, David; Erickson, Craig A.

doi:10.3390/brainsci9020018

Cited by 36 publications

(29 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Social avoidance encompasses behaviors such as social isolation, social escape behaviors, and gaze avoidance that distance the individual from his/her social counterparts. Behavior problems concerning caregivers of children with FXS ( n = 439) include anxiety, tantrums, and aggression while the participants also want drug treatment to reduce anxiety, address social anxiety, tantrums, and aggression [4]. Estimates of prevalence suggest that FXS affects approximately 1.4 in 10,000 males and 0.9 in 10,000 females, making it the most common heritable cause of intellectual disability [5].…”

Section: Introductionmentioning

confidence: 99%

A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome

Heussler

Cohen²,

Silove

et al. 2019

J Neurodevelop Disord

View full text Add to dashboard Cite

Background Fragile X syndrome (FXS) is characterized by a range of developmental, neuropsychiatric, and behavioral symptoms that cause significant impairment in those with the disorder. Cannabidiol (CBD) holds promise as a potential treatment for FXS symptoms due to its safety profile and positive effects on a number of emotional and behavioral symptoms associated with FXS. The aim of the current study was to evaluate the safety, tolerability, and initial efficacy of ZYN002, a transdermal CBD gel, in a pediatric population with FXS. Methods Twenty children and adolescents (aged 6–17 years) with a diagnosis of FXS (confirmed through molecular documentation of FMR1 full mutation) were enrolled in an open-label, multi-site, trial of ZYN002. Transdermal CBD gel was administered twice daily for 12 weeks, titrated from 50 mg to a maximum daily dose of 250 mg. The primary efficacy endpoint was change from screening to week 12 on the Anxiety, Depression, and Mood Scale (ADAMS). Secondary endpoint measures included the Aberrant Behavior Checklist—Community for FXS (ABC-C FXS ), Pediatric Anxiety Rating Scale (PARS-R), Pediatric Quality of Life Inventory (PedsQL™), three Visual Analogue Scales (VAS), and the Clinical Global Impression Scale—Severity (CGI-S) and Improvement (CGI-I). Results The majority of treatment-emergent AEs (reported by 85% of participants) were mild in severity (70%), and no serious adverse events were reported. There was a statistically significant reduction in ADAMS total score from screening to week 12 and significant reductions on nearly all other secondary endpoints, including all ADAMS subscales (except depressed mood), all ABC-C FXS subscale scores (e.g., social avoidance, irritability), PARS-R total severity score, and PedsQL total score. Conclusions ZYN002 was well tolerated and produced clinically meaningful reductions in anxiety and behavioral symptoms in children and adolescents with FXS. These findings support further study of ZYN002 in a randomized, well-controlled trial for the treatment of behavioral symptoms of FXS. Trial registration ANZCTR, ACTRN12617000150347 Registered 27 January 2017

show abstract

Section: Introductionmentioning

confidence: 99%

A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome

Heussler

Cohen²,

Silove

et al. 2019

J Neurodevelop Disord

View full text Add to dashboard Cite

show abstract

“…Ten authors described the challenges of caring for a child with FXS (19,20,(22)(23)(24)(25)(26)(27)(28)(29). Throughout childhood and adolescence, parents described challenges in dealing with behavioral difficulties, especially when skills like speaking and communication are compromised.…”

Section: Challenges Of Caring For a Child With Fxsmentioning

confidence: 99%

“…Parents also described concerns about their children's ability to live independently. More so, academic performance, self-care and behavior were the main concern for parents taking care of male FXS patients while social issues were the main concern for parents of females FXS patients (29). Worries about the future and dealing with behavioral challenges ultimately reduced the quality of life of families.…”

Section: Challenges Of Caring For a Child With Fxsmentioning

confidence: 99%

Lived Experiences of Fragile X Syndrome Caregivers: A Scoping Review of Qualitative Studies

et al. 2020

View full text Add to dashboard Cite

Fragile X Syndrome (FXS) is the most common x-linked monogenic cause of Intellectual Disability (ID) and Autism Spectrum Disorder (ASD). Taking care of children with ID is challenging and overwhelming due to the multiple facets of caregiving. This scoping review aimed at summarizing the qualitative literature on the experiences of families living with FXS, identify key themes and determine the gaps in the extant literature. We conducted a literature search in May 2019 using four databases; PubMed, Web of Science, African-Wide-Information, and Scopus. The keywords used in our search strategy were associated with caregivers, lived experiences, FXS, and qualitative research. All English language articles with full-text reporting were included. Studies associated with other neurodevelopmental conditions and quantitative studies were excluded. We identified 12 out of 203 articles that described the lived experiences of families with FXS. Most articles originated from the United States of America and mothers were the main caregivers. We summarized our findings into four major themes which are; grief experiences, challenges of living with FXS, coping mechanisms and the need to plan for future outcomes. This scoping review highlights the scarcity of qualitative FXS literature in the African population and frustrations endured by families with FXS due to the low knowledge of FXS by healthcare workers. More research is needed to evaluate the impact of living with FXS in males and fathers.

show abstract

“…Additionally, people with ASD have an increased risk of developing MDD by the time they are 30 years old compared to people without ASD 20 . Moreover, caretakers of people with FXS identify mood and depression as a priority for treatment development 21 . While FMRP is extensively characterized in the context of ASD, its role in MDD and MDD treatments is unclear.…”

Section: Introductionmentioning

confidence: 99%

Role of FMRP in rapid antidepressant effects and synapse regulation

Heaney

Namjoshi

Uneri

et al. 2020

Preprint

View full text Add to dashboard Cite

Rapid antidepressants are novel treatments for major depressive disorder (MDD) and work by blocking N-methyl-aspartate receptors (NMDAR), which, in turn, activate the protein synthesis pathway regulated by mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Our recent work demonstrates that the RNA-binding protein Fragile X Mental Retardation Protein (FMRP) is downregulated in dendrites upon treatment with a rapid antidepressant. Here, we show that the behavioral effects of the rapid antidepressant Ro-25-6981 requires FMRP expression and promotes differential mRNA binding to FMRP in an mTORC1-dependent manner. Further, these mRNAs are identified to regulate transsynaptic signaling. Using a novel technique, we show that synapse formation underlying the behavioral effects of Ro-25-6981 require GABABR-mediated mTORC1 activity in WT animals. Finally, we demonstrate that in a clinically relevant animal model of Fragile X Syndrome (FXS), which lacks FMRP expression, GABABR activity is detrimental to the effects of Ro-25-6981. These effects are rescued when GABABRs are blocked in addition to treatment with Ro-25-6981, indicating that rapid antidepressants alone may not be an effective treatment for people with FXS and MDD.

show abstract

Voice of People with Fragile X Syndrome and Their Families: Reports from a Survey on Treatment Priorities

Cited by 36 publications

References 14 publications

A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome

A phase 1/2, open-label assessment of the safety, tolerability, and efficacy of transdermal cannabidiol (ZYN002) for the treatment of pediatric fragile X syndrome

Lived Experiences of Fragile X Syndrome Caregivers: A Scoping Review of Qualitative Studies

Role of FMRP in rapid antidepressant effects and synapse regulation

Contact Info

Product

Resources

About