Qualitative metasummary: Parents seeking support related to their TGNC children.

Background: Parents seek support on behalf of their transgender and gender nonconforming (TGNC) children. Previous qualitative studies explore the types of support parents seek inside and outside of healthcare settings. Healthcare providers often remain unprepared to effectively provide gender-affirming services to TGNC children and their accompanying parents and may benefit from learning about the support seeking experiences of parents with TGNC children. Aims: This paper summarized qualitative research studies that address the topic of parents seeking support on behalf of their TGNC children. We produced this report for healthcare providers to review to enhance gender-affirming services for parents and TGNC children. Methods: This paper outlines a qualitative metasummary of studies from the United States or Canada with data collected from parents of TGNC children. Data collection included the steps of journal runs, database searches, reference checks, and area scans. Data analysis involved the steps of extracting, editing, grouping, abstracting, and calculating the intensity and frequency effect sizes for finding statements from qualitative research study articles. Results: The results of this metasummary yielded two primary themes, six subthemes, and 24 total findings. The first primary theme of seeking guidance had three subthemes: educational resources, community networks, and advocacy efforts. The second primary theme of seeking healthcare had three subthemes: healthcare providers, mental healthcare, and general healthcare. Discussion: These findings provide information healthcare providers can use to inform their practice. These findings also highlight the importance of providers working collaboratively with parents when serving TGNC children. This article concludes with practical tips for providers.

Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: A randomised, double-blind, placebo-controlled phase 1a trial.

BACKGROUND: Synucleinopathies such as Parkinson ́s disease (PD), Dementia with Lewy bodies (DLB) and Multiple System Atrophy (MSA) are characterized by deposition of misfolded and aggregated α-synuclein. Small aggregates (oligomers) of α-synuclein have been shown to be the most relevant neurotoxic species and are targeted by anle138b, an orally bioavailable small molecule compound which shows strong disease-modifying effects in animal models of synucleinopathies. METHODS: Anle138b was studied in a single-centre, double-blind, randomised, placebo-controlled single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy subjects. Eligible participants were randomly assigned (1:1 for sentinel subjects and 1:5 for main group) to placebo or anle138b (dose range 50 mg to 300 mg per day), respectively. In addition, the effect of food on the pharmakokinetics of anle138b in healthy subjects was examined in doses of 150 mg per day. Participants were randomized to treatment sequence (fed→fasted) or (fasted→fed). Treatment was administered orally in hard gelatine capsules containing either 10 mg or 30 mg of anle138b or excipient only. The primary endpoints were safety and tolerability, the secondary endpoint was pharmakokinetics. Data from all randomized individuals were evaluated. CLINICALTRIALS: gov-identifier: NCT04208152. EudraCT-number: 2019-004218-33. FINDINGS: Between December 17th, 2019 and June 27th, 2020 196 healthy volunteers were screened and 68 participants were enrolled. Of these, all completed the study per protocol. There were no major protocol deviations. Adverse events in this healthy volunteer trial were mostly mild and all fully recovered or resolved prior to discharge. From baseline to completion of the trial no medically significant individual changes were observed in any system organ class. Already at multiple doses of 200 mg, exposure levels above the fully effective exposure in the MI2 mouse Parkinson model were observed. INTERPRETATION: The favourable safety and PK profile of anle138b in doses resulting in exposures above the fully effective plasma level in a mouse Parkinson model warrant further clinical trials in patients with synucleinopathies. FUNDING: This study was funded by MODAG GmbH and by the Michael J. Fox foundation for Parkinson's Research.