bims-curels 2026-05-03 papers

Issue of 2026–05–03
six papers selected by
Cure Mito Foundation

Mol Psychiatry. 2026 Apr 29.

Adeno-Associated virus-based approaches for mitochondrial diseases: advances and challenges.

Samantha Corrà, Valeria Balmaceda, Carlo Viscomi.

Mitochondrial diseases, caused by mutations in either mitochondrial or nuclear DNA, are highly complex genetic disorders characterized by faulty oxidative phosphorylation. Adeno-associated virus (AAV)-based gene therapy with its broad and customizable tissue tropism achieved through natural and engineered serotypes offers a highly effective platform for delivering therapeutic genes to affected tissues. However, the intricate genetics and biology of mitochondria present unique challenges for the development of AAV-based therapies. While gene replacement therapy remains a viable strategy for correcting nuclear gene defects, mutations in mtDNA require specialized approaches, such as mitochondrially targeted, RNA-free base editors and nucleases capable of precise editing within the mitochondrial genome. As an alternative, allotopic expression, which involves expressing mitochondrial genes from the nuclear genome, is currently being evaluated in clinical trials but remains controversial, due to issues related to mitochondrial import and functional integration in the respiratory complexes. The clinical translation of AAV-mediated therapies for mitochondrial diseases still confronts several interrelated challenges, including efficient targeting of multiple affected organs, scalable and cost-effective vector manufacturing, and minimizing vector-associated toxicity. By integrating advanced genome editing technologies with sophisticated vector engineering and delivery strategies, AAV-based gene therapy stands as a transformative approach for addressing the broad and heterogeneous spectrum of primary mitochondrial disorders. Continued progress in overcoming current biological and technical barriers will be essential to realize the full therapeutic potential of AAVs.

DOI: https://doi.org/10.1038/s41380-026-03570-y

Neurobiol Dis. 2026 Apr 24. pii: S0969-9961(26)00157-9. [Epub ahead of print]224 107412

Analysis of mitochondrial DNA heteroplasmy in sporadic ALS suggests technical limitations rather than disease association.

Philippe Codron, Valérie Desquiret, Delphine Prunier, Patrizia Amati-Bonneau, Viviane Nguefackngoune, Clara Rapenne, Louis Legoff, Julien Cassereau, Vincent Procaccio.

Mitochondrial DNA (mtDNA) has received increasing attention in amyotrophic lateral sclerosis (ALS) following the recent report of recurrent low-heteroplasmy mtDNA variants in patients. Here, we performed mtDNA analysis on an independent cohort of 20 sporadic ALS patients using an in-house next-generation sequencing pipeline designed for diagnostics. Using standard filters, none of the previously reported low-heteroplasmy mtDNA variants were detected. These variants only appeared in the low-quality data and were present at similar rates in a large reference population without ALS, localizing to homopolymeric regions that are prone to sequencing errors. Our findings suggest that these low-level mtDNA variants are a result of the technical limitations of short-read next-generation sequencing rather than being associated with the disease.

Keywords: Amyotrophic lateral sclerosis; Mitochondria; Mitochondrial DNA

DOI: https://doi.org/10.1016/j.nbd.2026.107412

Ned Tijdschr Geneeskd. 2026 Apr 28. pii: D8882. [Epub ahead of print]170

[Looking at care differently; a plea for art in medical education].

Laura Alexandra van der Woude, Marco Antonio de CarvalhoFilho, Suzanne Festen.

Personcentered care is essential for a futureproof healthcare system, yet its implementation lags behind due to a predominantly diseasecentered perspective. Traditional educational approaches appear insufficient to shift this mindset. Perspective change rarely results from information transfer alone; it arises through personal experience. Art brings this experiential dimension into medical education and fosters a different way of seeing care. It helps healthcare professionals deal with complexity, uncertainty, and recognize their own assumptions. In the Netherlands, several artbased initiatives exist within medical training, including Medical Education Empowered by Theater for shared decisionmaking (MEET SDM). MEET SDM is an experiential training designed to promote perspective change for learning shared decisionmaking. Through reflexive dialogue, theater- and improvisational exercises, participants experience that shared decisionmaking requires genuine attention to another's perspective, connection, and (non)verbal presence. Participants reported concrete personcentered behavioral changes in clinical encounters, positively influencing the doctor-patient relationship. Artbased education contributes to overcoming the disease-centered perspective and supports a different way of viewing oneself, one's professional role, and the patient.

Eur Arch Paediatr Dent. 2026 Apr 25.

Parental expectations regarding the announcement of a diagnosis of a rare oral disease: a qualitative study in Marseille, France.

I Blanchet, C Tardieu, F Michel, A Camoin.

PURPOSE: To explore parents' expectations regarding the disclosure of an oligodontia diagnosis in dental practice and analysing them through the lens of core bioethical principles (principlism).
METHODS: A qualitative interview study was conducted with parents of children diagnosed with oligodontia, all of whom had attended at least one consultation at a French specialist centre. Interviews were analysed using reflexive thematic analysis.
RESULTS: The study sample consisted of 18 parents who reported frequent dissatisfaction with the way the diagnosis was disclosed. The findings suggest that a two-step disclosure process (initial diagnosis and specialist follow-up) is commonly used. Parents valued this approach, as well as referral to patient associations. They recommended this two-step process to allow time for initial emotional adjustment and subsequent discussion. Their expectations focused on clarity of information, the provision of written materials, emotional support, and sufficient consultation time. They emphasised the need for a caring attitude, confidentiality, and tailored communication that includes both the child and the parents. A tension may arise between parental desires to protect their child and the child's right to participate.
CONCLUSION: Effective disclosure of oligodontia requires more than clinical expertise; it demands a caring, ethically informed approach that balances clarity and empathy, as well as adequate time and resources, acknowledges uncertainty, and navigates the complex role of the child as a participant in their own care. The challenge, therefore, is to find the right balance between the duty of beneficence, the principle of non-maleficence, and the recognition of individual autonomy. Communication skills are essential for aligning clinical practice with parental expectations. These findings, although rooted in the context of a rare dental disease, have broader implications for improving communication in dentistry.

Keywords: Communication; Ethics; Oligodontia; Paediatric dentistry; Parents’ expectations; Qualitative study

DOI: https://doi.org/10.1007/s40368-026-01209-8

Drug Discov Today. 2026 Apr 24. pii: S1359-6446(26)00087-5. [Epub ahead of print] 104682

Regulatory innovation for drug repurposing: Ten proposals to accelerate access and safety.

Sara Pintado, Adelaide Fernandes, Esther A M Bührman, Joanna IntHout, Sofia Oliveira-Martins.

Despite increasing efforts and incentives to address the critical lack of treatments for rare diseases, a substantial gap persists between patient needs and available therapies. Drug repurposing is a promising strategy in this field; nevertheless, it has not yet translated into a substantial increase in approved medicines. Although several EU regulatory pathways exist, none is tailored to drug repurposing, resulting in a complex landscape, particularly for nonprofit organisations. While there is no silver bullet, this article presents ten regulatory proposals to foster dialogue with decision-makers to tackle bottlenecks in areas of unmet medical need through a collaborative model with aligned incentives for all stakeholders. These proposals are based on published literature and the authors' experience in the SIMPATHIC project.

Keywords: European regulatory framework; drug approval; drug repurposing; orphan drugs; policy recommendations; rare diseases; real-world evidence

DOI: https://doi.org/10.1016/j.drudis.2026.104682

J Particip Med. 2026 May 01. 18 e74436

Advancing the Science of Patient Input in Drug Research and Development.

Marilyn A Metcalf, Henrietta Awo Osei-Anto, Thomas J Sharpe, Luther T Clark, Carolyn K Shore.

The integration of patient input into drug research & development (R&D) enables the production of medicines that better meet the needs of patients. While momentum for advancing the science of patient input has continued to grow, there remain a host of barriers to full implementation and integration of systematic approaches for collecting and using robust and meaningful patient input data to inform decision-making. To help address these barriers, the Advancing the Science of Patient Input Action Collaborative (the collaborative), an activity associated with the National Academies of Sciences, Engineering, and Medicine (National Academies) Forum on Drug Discovery, Development, and Translation, organized a multi-stakeholder endeavor to identify and address key barriers to implementation through a series of information-gathering efforts. The collaborative engaged a wide range of perspectives to seek out practical paths forward to better align drug discovery, development, and regulation with patient priorities for disease management and treatment. Collaborative participants focused on three overarching research priorities which, if effectively addressed, would help advance the science of patient input: 1) understanding the patient experience over the course of a given disease or medical condition, 2) capturing the patient perspectives and priorities on benefit-risk, and 3) incorporating patient input into clinical trial design and continuous improvement. Addressing these research priorities would help decision makers shift away from using patient input in particular cases or for one-off applications and towards the integration of patient input as part of everyday medical research and practice. Building upon existing guidances and strategies, and sharing lessons learned from use cases, a comprehensive patient input framework would serve as a critical step towards reimagining and enriching the science of patient input throughout the drug R&D process, enabling a future in which medicines more fully meet the needs of patients.

Keywords: clinical research; clinical trials; drug research and development; patient input; patient-centered

DOI: https://doi.org/10.2196/74436