bims-curels 2023-10-08 papers

Issue of 2023–10–08
six papers selected by
Cure Mito Foundation

Orphanet J Rare Dis. 2023 Oct 02. 18(1): 307

Wide diagnostic and genotypic spectrum in patients with suspected mitochondrial disease.

Kristina Grigalionienė, Birutė Burnytė, Laima Ambrozaitytė, Algirdas Utkus.

BACKGROUND: Mitochondrial Diseases (MDs) are a diverse group of neurometabolic disorders characterized by impaired mitochondrial oxidative phosphorylation and caused by pathogenic variants in more than 400 genes. The implementation of next-generation sequencing (NGS) technologies helps to increase the understanding of molecular basis and diagnostic yield of these conditions. The purpose of the study was to investigate diagnostic and genotypic spectrum in patients with suspected MD. The comprehensive analysis of mtDNA variants using Sanger sequencing was performed in the group of 83 unrelated individuals with clinically suspected mitochondrial disease. Additionally, targeted next generation sequencing or whole exome sequencing (WES) was performed for 30 patients of the study group.
RESULTS: The overall diagnostic rate was 21.7% for the patients with suspected MD, increasing to 36.7% in the group of patients where NGS methods were applied. Mitochondrial disease was confirmed in 11 patients (13.3%), including few classical mitochondrial syndromes (MELAS, MERRF, Leigh and Kearns-Sayre syndrome) caused by pathogenic mtDNA variants (8.4%) and MDs caused by pathogenic variants in five nDNA genes. Other neuromuscular diseases caused by pathogenic variants in seven nDNA genes, were confirmed in seven patients (23.3%).
CONCLUSION: The wide spectrum of identified rare mitochondrial or neurodevelopmental diseases proves that MD suspected patients would mostly benefit from an extensive genetic profiling allowing rapid diagnostics and improving the care of these patients.

Keywords: Genetic diagnosis; Mitochondrial disease; Next generation sequencing; Variants; Whole exome sequencing; mtDNA; nDNA

DOI: https://doi.org/10.1186/s13023-023-02921-0

Nature. 2023 Oct 06.

Gene therapies for rare diseases are under threat. Scientists hope to save them.

Heidi Ledford.

Keywords: Business; Drug discovery; Gene therapy; Medical research; Society

DOI: https://doi.org/10.1038/d41586-023-03109-z

Res Involv Engagem. 2023 Sep 30. 9(1): 88

Youth and family involvement in the development of a plain language trial results communication tool: CommuniKIDS.

Ami Baba, Dawn P Richards, Maureen Smith, Nicole Pallone, Shelley Vanderhout, Matthew Prebeg, Ellen B M Elsman, Beth K Potter, Martin Offringa, Nancy J Butcher.

BACKGROUND: Pediatric trials are possible through voluntary participation of children, youth (age ≤ 18 years), and their families. Despite important arguments for trialists to provide trial progress or results, and evidence that participants desire it, this information remains rarely shared with youth and their families. Little guidance exists on how trialists can best communicate trial results back to participants and their families. Guided by Liabo et al.'s framework, we describe how we developed a pediatric-specific, "plain language summary" clinical trial results template called CommuniKIDS with an adult patient partner, family partner (parent), youth advisors, and parent advisors, taking into account their unique knowledge needs and preferences.
MAIN TEXT: Patient and Public Involvement (PPI) was integrated in the development of the CommuniKIDS template. In collaboration with Clinical Trials Ontario, we used a generic trial results template as a starting point. The core project leadership team included a patient partner and a family partner from project inception to completion. Five youth (ages 13-18 years) and eight parent advisors were consulted at each point of the development process through three virtual workshops conducted separately; youth workshops were led by a youth facilitator. During these workshops, advisors agreed on the importance and value of sharing trial results, and expressed their preferences on content, format, and timing of sharing trial results. PPI-led improvements included the addition of three new sections to the CommuniKIDS template: "at a glance," "side effects," and "next steps." We reflect on our PPI strategy in the context of five "values" and six "practicalities" identified as good PPI principles, and summarize lessons learned when collaborating with youth and families from this project.
CONCLUSION: Involvement of a patient partner, a family partner, youth advisors, and parent advisors in the development of CommuniKIDS was critical to create a clinical trial results template that is useful and relevant to its end-users. To our knowledge, CommuniKIDS is the first to meaningfully engage youth and parents as advisors and partners in developing a plain language summary results template for pediatric trial participants and their families. Our experience of co-developing CommuniKIDS demonstrates that meaningful PPI can be achieved in trial results communication and knowledge translation practices. This report provides resources for those seeking to involve youth and families in their initiatives and in meaningfully sharing trial results.

Keywords: Clinical trials; Family engagement; Patient and public involvement (PPI); Patient engagement; Plain language summary; Trial results; Youth engagement

DOI: https://doi.org/10.1186/s40900-023-00499-2

BMC Rheumatol. 2023 Oct 03. 7(1): 36

The student patient alliance: development and formative evaluation of an initiative to support collaborations between patient and public involvement partners and doctoral students.

Gwenda Simons, Rebecca Birch, Joanne Stocks, Elspeth Insch, Rob Rijckborst, Georgiana Neag, Heidi McColm, Leigh Romaniuk, Claire Wright, Bethan E Phillips, Simon W Jones, Arthur G Pratt, Stefan Siebert, Karim Raza, Marie Falahee.

BACKGROUND: While the integration of patient and public involvement (PPI) in clinical research is now widespread and recommended as standard practice, meaningful PPI in pre-clinical, discovery science research is more difficult to achieve. One potential way to address this is by integrating PPI into the training programmes of discovery science postgraduate doctoral students. This paper describes the development and formative evaluation of the Student Patient Alliance (SPA), a programme developed at the University of Birmingham that connects PPI partners with doctoral students.
METHODS: Following a successful pilot of the SPA by the Rheumatology Research Group at the University of Birmingham, the scheme was implemented across several collaborating Versus Arthritis / Medical Research Council (MRC) centres of excellence. Doctoral students were partnered with PPI partners, provided with initial information and guidance, and then encouraged to work together on research and public engagement activities. After six months, students, their PPI partners and the PPI coordinators at each centre completed brief surveys about their participation in the SPA.
RESULTS: Both doctoral students and their PPI partners felt that taking part in SPA had a positive impact on understanding, motivation and communication skills. Students reported an increased understanding of PPI and patient priorities and reported improved public engagement skills. Their PPI partners reported a positive impact of the collaboration with the students. They enjoyed learning about the student's research and contributing to the student's personal development. PPI coordinators also highlighted the benefits of the SPA, but noted some challenges they had experienced, such as difficulties matching students with PPI partners.
CONCLUSIONS: The SPA was valued by students and PPI partners, and it is likely that initiatives of this kind would enhance students' PPI and public engagement skills and awareness of patients' experiences on a wider scale. However, appropriate resources are needed at an institutional level to support the implementation of effective programmes of this kind on a larger scale.

Keywords: Discovery science; Doctoral students; Patient and public involvement; Rheumatic and musculoskeletal diseases.

DOI: https://doi.org/10.1186/s41927-023-00359-2