This is just the beginning!
Only with your support is treatment possible.
Giving Strength relies on our academic and industry partners to move the needle on the crucial research necessary to find a treatment for SELENON-RM. Below is a list of current and completed projects:
Active Projects
Summary: SELENON-RM is characterized by weakness of the diaphragm, the primary skeletal muscle responsible for breathing. Diaphragmatic dysfunction can result in reduced oxygen levels (hypoxia), leading to cellular stress and tissue damage. In this project, mice lacking SELENON expression will be exposed to intermittent hypoxia to assess the impact of low oxygen levels on the diaphragm and other respiratory muscles. Once characterized, this model will be used to evaluate the efficacy of therapeutic candidates for SELENON-RM.
Project funded by Penny’s Promise, Toronto, and managed by Giving Strength.
Summary: Cell-based phenotypic assays, which measure detectable features of a disease and how these features are affected by drug treatments, are a key component of early drug discovery. Cell lines are the building blocks of these assays. Currently, the most useful SELENON-RM cell lines are derived directly from patients or mouse models and are consequently challenging to obtain, insufficient in number for large-scale studies or broad distribution, and in the case of murine cells, may have limited relevance to some human disease characteristics. The development of physiologically relevant and widely accessible cell lines therefore represents a critical unmet need in SELENON-RM research. In this project, fibroblasts obtained from skin samples from SELENON-RM patients and unaffected controls will be genetically engineered for indefinite propagation and to allow conversion into muscle cells, creating a sustainable supply of biologically meaningful cells for research and assay development. The modified cells will be made available to the global research community through a nonprofit biorepository.
Summary: Dr. Barraza-Flores has accepted multi-year salary support from Giving Strength to continue her highly productive research in the laboratory of Dr. Alan Beggs at Boston Children’s Hospital. This project will involve the development of a cutting-edge, high-throughput cell painting assay capable of comparing approximately 6,000 different features in cells from SELENON-RM patients and disease models against healthy controls to identify disease-associated abnormalities. Once optimized, the platform will be used to screen repurposable drug libraries for compounds that can restore healthy phenotypes in SELENON-RM cells.
Summary: This personalized medicine study collected eight sequential samples from patient–control pairs, each consisting of an affected individual and an unaffected, gender-matched family member. Gene expression profiles were compared within each pair, and the resulting data were analyzed using a machine-learning platform to identify repurposable drugs capable of shifting the patient phenotype toward that of the control. Pending final data review, this study could be expanded to include additional patients. Top hits will be tested in SELENON-RM disease models.
Summary: Dr. Barraza-Flores, who recently completed her postdoctoral training in the laboratory of Dr. Alan Beggs, has accepted multi-year salary support from Giving Strength to advance her highly productive research on SELENON-RM. Her work will focus on identifying and characterizing tissue, cellular, and molecular changes associated with compensatory homeostasis and regeneration in SELENON-RM muscle. These studies will utilize skeletal muscle samples from both pediatric and adult patients, as well as from mouse models.
Summary: Disrupted intracellular calcium signaling is thought to contribute to the pathophysiology of SELENON-RM, although the specific mechanisms remain unclear. In this project, the Yang laboratory will develop highly sensitive constructs designed to monitor calcium dynamics in the immediate vicinity of key calcium-regulating proteins and organelles essential for muscle function. This platform will enable detailed investigation into the root causes of calcium dysregulation in SELENON-RM. Future studies will involve adapting the assay for high-throughput screening of drug repurposing and small molecule libraries to identify compounds capable of improving calcium regulation in SELENON-RM.
Summary: Gene expression data were generated by RNA sequencing (RNA-Seq) of numerous SELENON-RM patient samples and unaffected controls. These datasets will undergo rigorous statistical processing and comprehensive bioinformatic analyses to identify both shared and patient-specific, disease-associated signatures. This study may enable the discovery of exploratory, disease-relevant biomarkers for clinical assessment and could also reveal new therapeutic targets to guide future drug discovery efforts. This project is being carried out in collaboration with Dr. Pamela Barraza-Flores from the Beggs Laboratory at Boston Children’s Hospital.
Summary: The Zito laboratory has identified a novel biochemical pathway in SELENON-RM cells that, if therapeutically targeted, might help reduce disease pathology. Funding from Giving Strength will support the salary of Dr. Serena Germani, a postdoctoral researcher dedicated to defining the role of this pathway in the development and progression of SELENON-RM.
Summary: The Thomas laboratory specializes in the molecular mechanisms underlying muscle diseases and has extensive expertise in examining direct protein–protein interactions using Fluorescence Resonance Energy Transfer (FRET). In this project, Dr. Thomas, working in collaboration with the University of Minnesota’s Biophysical Technology Center and Dr. Ester Zito, will develop a FRET-based assay to determine whether ERO1 interacts directly with the calcium pump SERCA, a key regulator of muscle function. If a direct interaction is confirmed, the high-throughput assay will be used to screen a repurposable drug library to identify compounds that disrupt the interaction, with the goal of improving SELENON-RM phenotypes. As needed, the platform will also support screening of a larger library of chemical compounds.
Summary: The Zito laboratory has shown that elevated levels of the protein ERO1, which is upregulated under certain conditions of cellular stress, exacerbate pathological features of SELENON-RM in cellular and animal models. This project will confirm whether ERO1 expression is similarly increased in muscle tissue derived from SELENON-RM patients and will pursue the identification of potent ERO1 inhibitors as potential therapeutic candidates for the disease. Previous work on this project was co-funded by Giving Strength and Cure CMD (2023–2024).
Summary: Researchers at Radboud University Medical Center in the Netherlands, including Dr. Nicol Voermans and Dr. Corrie Erasmus, with support from PhD candidate Ilse de Laat, MS, are leading a five-year natural history study of SELENON-RM called the Extended LAST STRONG study. This effort involves detailed documentation and analysis of disease progression across neurological, musculoskeletal, and respiratory domains. Giving Strength, alongside other nonprofit organizations, is providing financial support for the collection of five-year clinical data and the analysis and publication of three- and five-year data from this study.
Co-funded with: Prinses Beatrix Spierfonds and Stichting Voor Sara.
On Hold Projects
Summary: This project was designed to evaluate whether enhancing the activity of the calcium pump SERCA could mitigate disease phenotypes in SELENON-RM skeletal muscle cells. If proof of concept were established, potential SERCA activators would be identified and evaluated in more advanced SELENON-RM models. The project was initiated but is currently on hold pending the availability of cell lines more suitable to the assay platform.
Completed Projects
Summary: Financial support was provided to the Beggs laboratory over a two-year period, enabling progress across multiple initiatives. These efforts included development of a gene therapy construct designed by Dr. Behzad Moghadaszadeh to deliver a full-length, functional version of the SelN protein to skeletal muscle along with a muscle-injury model for evaluating therapeutic efficacy; identification of zebrafish phenotypes associated with SELENON mutations and preliminary drug testing in this model, led by Dr. Pamela Barraza-Flores; and many additional laboratory studies aimed at elucidating the cellular mechanisms underlying SELENON-RM.
Summary: The metabolic pathways responsible for generating cellular energy in the form of ATP appear to be dysregulated in cells from patients with SELENON-RM. This project established a high-throughput drug-screening assay to identify candidate therapeutics capable of restoring normal ATP levels and reducing cellular stress in patient-derived muscle cells. A library of repurposable drugs was screened, resulting in the preliminary identification of several potential hits, which will be further investigated in future studies. Preliminary findings from this work were presented in October 2025 at the World Muscle Society Congress in Vienna.
Co-funded with: Cure CMD