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Research Update: Collagen 6

Updated: May 29

A group of people wearing conference lanyards in a meeting room, sitting and standing in rows, posing for the photo in front of two screens displaying the title, “COLLAGEN VI International Research Summit.”

We are honored to support groundbreaking discoveries in Collagen 6-Related Dystrophies (COL6-RD), thanks to our generous supporters and advocacy partners.

Research Project Updates

Jeanette Erdmann and Franziska Haarich, Further steps toward an RNA-based therapy for COL6-RD. Funding: 2022-2024. Co funded with Muscular Dystrophy Canada. This project focuses on developing a gene-silencing therapy for glycine mutations, which account for about 30% of disease-causing mutations in COL6-RD. Glycine mutations are dominant-negative, meaning that changes in one of two gene copies interferes with normal protein function. The goal of the project is to successfully silence the mutated gene copy using a genetic tool called CRISPRoff, a new addition to the portfolio of gene therapies that leaves the DNA sequence unchanged, unlike traditional CRISPR that uses a scissor-like function to remove faulty DNA. This technique has the potential to tackle different mutations using the same tool rather than only targeting individual mutations.

So far, the team has achieved a 20% reduction (knockdown) of the mutant allele, with next steps to tune up this methodology, increasing efficiency and establishing proof of concept.


Francesco Saverio Tedesco, Advanced human myo-fibrogenic 3D models for COL6 disease modeling and therapy development. Funding: 2022-2024. Co funded with Muscular Dystrophy Canada. The focus of this project is to develop 3D muscle models to study ECM-muscle cell interactions using cells from both healthy and COL6-affected donors. The ECM, or Extracellular Matrix, provides a 3D network of stability for cells while regulating cell development and regeneration. Using these novel models, the team intends to mimic key aspects of dysfunction in COL6-RD to facilitate the development of new therapies for all COL6-RDs.

So far, the team has successfully created a 3D model that imitates the interaction between muscle fibers and the ECM, as well as some of the problems associated with COL6-RD, such as disorganized collagen, muscles that cannot stretch, and reshaping of the ECM.

Next steps are to test the model with cells derived from affected individuals, and further characterize and optimize the model. Once they have produced a number of robust readouts from myo-fibrogenic 3D cultures, they will explore this model’s potential for use in therapeutic development. These preliminary studies will be incorporated into a larger consortium of multidisciplinary research to develop therapies for COL6-RD and three other neuromuscular conditions, called MAGIC (Next-generation Models And Genetic TherapIes for Rare NeuromusCular Diseases). This project can be followed on X, Linkedin and YouTube. Cure CMD is among four patient-advocacy organizations, eight academic institutions, and four biotech companies that comprise this consortium. Our role is to provide representation of the affected community and disseminate results of the project to stakeholders.


Vittoria Cenni, Targeting Primary Cilium-Related Molecular Pathways to Correct Tendon Cell Defects in Collagen VI Congenital Muscular Dystrophies. Funding: 2023-2025. Co funded with AFM-Telethon. This project is a continuation of work previously funded by Cure CMD to characterize the function of joint contractures in COL6-RD, which found that some of the mechanisms in COL6-mutated cells (ECM assembly, cell polarization, autophagy) are, in part, controlled by primary cilium proteins (PC). PC are antenna-like structures of the cell that capture external signals and convert them into cellular responses. When the PC is defective, cell survival is impaired.

Building from preliminary data derived in the previous project, which demonstrated structural and functional differences of PC in the tendon cells of COL6-affected individuals, the research team is using tendon cell cultures from healthy and affected individuals to better understand the response of PC to metabolic and mechanical stress, alterations of PC-autophagy cross-talk, and to test the efficacy of specific compounds that alter PC-related molecular pathways as a potential treatment to address contractures.


Carsten Bönnemann and Veronique Bolduc, Directed evolution of adeno-associated virus (AAV) capsids for effective beneficial delivery to the muscle fibro-adipogenic progenitors (FAPS). Funding: 2021-2024. Co funded with Noelia Foundation This project’s goal is to identify an Adeno-Associated Virus (AAV) that can be used to deliver gene therapies for COL6-RD. AAVs use keys, or protein flakes, exposed at their surface, to deliver cargo to specific organs or cell types in the body. Each type of AAV has a different set of keys. Most types of AAV being developed for neuromuscular conditions have keys to target skeletal muscle cells. However, intermingled with muscle cells is a type of support cell for muscles called fibro-adipogenic progenitors (FAPs), which are the main source of Collagen 6 production. Thus, we must identify an AAV that specifically targets (or has keys for) FAPs, in order to deliver an effective gene therapy for this CMD subtype.

The research team is screening a library of 3,612 different AAVs, each identified by a unique barcode, using a mouse model in which FAP cells are highlighted fluorescent green. Researchers can then isolate FAPs, by selecting the green cells, to identify whether the AAVs being tested are being delivered to FAPs.

So far, three of the screened AAVs have promise. The team is now performing further analysis to identify the amino acid positions that determine FAP targeting. This work is fundamental to advancing AAV-based therapies for COL6-RD.


A. Reghan Foley, Biomarker Discovery Project Using Samples from Patients with COL6 and LAMA2 Related CMDs. Funding: 2023-2024. Co funded with COL6 Fund, Noelia Foundation, LAMA2 France, ImpulsaT, Voor Sara, and CMD Turkey. This project is focused on identifying biomarkers for COL6 and LAMA2-RD using samples collected at the NIH from affected individuals. Biomarkers are biological “markers” that indicate a particular process of disease, important in measuring changes from a potential treatment in future clinical trials.

The INFANT Centre of the University College Cork, Ireland, has expertise in microRNA and proteomics biomarker research, and hosts a large cohort of bio samples from unaffected infants and children. Dr. Foley will use this bio repository as age and weight-matched controls for our community’s contributed samples, and will work with these experts to discover biomarkers COL6 and LAMA2. The first update is expected before the end of this year, so stay tuned!


All these projects, and others, were presented at a recent symposium hosted in the largest biotech hub in Spain. You can view the session program, summary and image gallery here.

See Cure CMD's full research grant portfolio here, and learn more about Cure CMD's research strategy here.


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