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Congenital Muscular Dystrophy Research
Ensuring that the research we fund is responsive to the affected community's needs and priorities
Research Strategy

Scientific research provides the foundation for understanding the causes and course of disease, and provides the opportunity to develop the tools necessary for establishing treatments that will slow, stop, or even reverse CMD symptom progression.
 
Everyone living with a congenital muscular dystrophy has unmet needs, and addressing those needs is at the core of
Cure CMD’s mission. We identify scientists and clinicians from around the world with a wide variety of expertise to remove treatment roadblocks, building a rich and adaptable research environment that capitalizes on new technologies as they arise.

We shepherd CMD research growth and breakthroughs and monitor advances in other neuromuscular conditions that could impact our own progress, continually refining priorities that are responsive to the needs of our affected community.

 

We participate in, and often host scientific meetings that share and interrogate research progress while communicating the needs of our affected community to researchers so that their priorities are aligned.

We encourage the interest and eagerness of young scientists, encouraging them to continue careers focused on CMD research after completing their fellowships.

Our Scientific Director stays abreast of the latest research publications, to better understand and incorporate scientific progress and breakthroughs into our research plan, and identify synergies between labs working in similar areas.

Perhaps most importantly, we maintain a continuous dialogue with the CMD community and expert clinicians, to understand the evolving needs and priorities of affected individuals, ensuring that we continue to fund the most promising research and clinical developments through our patient-centered vision.

None of this happens without our incredible advocacy partners and your financial support. we hope you'll join our mission to fund research toward treatments and provide educational and engagement programming for the congenital muscular dystrophy community.

Research Priorities

 

  • Natural History Studies (NHS). A fundamental piece of clinical trial readiness, NHS provide information about symptom progression and adverse events associated with each CMD subtype, ultimately identifying functional outcome measures for clinical trials, that along with biomarkers, provide measurable signs of how an intervention may impact disease progression and whether it slows or halts that progression and improves symptoms. Clinical trials cannot happen without NHS.

  • Research Tools. Cure CMD aims to fund the development and discovery of research tools that can be applied across all subtypes, such as patient-derived cell and animal models.

  • Biomarker Discovery Programs. Biomarkers are objective measures of biological processes that happen as a result of disease or treatment of that disease. Establishing biomarkers will aid in the development of outcome measures and a greater chance that regulators will approve clinical trial applications.

  • Basic Research. While we have learned a great deal about the underlying causes of CMD, new technologies are now allowing researchers to better understand and model disease mechanisms, triggers, and pathways. So sometimes, we still need to fund basic science to better inform the work to identify treatments.

  • Translational Research. Translating the lessons learned from basic research, pre-clinical studies, and NHS, translational research is the work of translating this valuable knowledge into real therapies -- bringing pharmaceutical companies, regulators and those living with CMD to the table.

  • Genetic Modifiers as Therapeutic Targets. Strong evidence supports the idea that affected individuals with the same mutation(s) often present with different symptoms, severity, and disease progression. This suggests that other genes may have an impact on protein production that directs muscle function. Discovery of genes that modify the presentation and evolution of disease is a new way to discover novel targets for therapeutic development.

Community Support Initiatives

  • Congenital Muscle Disease International Registry. A critical element of the research pipeline and a means for recruiting clinical study and trial participants, this tool offers the best way for affected individuals and their caregivers to directly participate in research, by sharing information about their diagnosis and lived experience with scientists working to identify treatments.

  • Care Guidelines. Beginning in 2024, Cure CMD and our advocacy partners will provide critical support to a global team of CMD experts to re-write care guides that are subtype-specific.

  • Education & Engagement Content. While scientists continue to work toward treatments, Cure CMD provides a number of opportunities for community members to learn about research, care standards, and ways to improve quality of life.

  • Community Stories & Blog. Community-focused content, written for and by affected individuals, caregivers, and allies - reflecting the voices of the CMD community. 

  • Cure CMD Mobile App. Our mobile app is now several years old, and needs a refresh! This app provides convenient, comprehensive, and searchable information for families, caregivers, affected individuals, and healthcare professionals when they most need it.

While all of these initiatives are invaluable to the entire CMD community, each subtype also has specific characteristics inherent to their genetic cause, requiring subtype-specific research plans. Stay tuned for updates as we are re-evaluating each subtype's priorities in 2024.

CMD Subtype Priorities (updates coming in February 2024)


With support from our leading CMD experts, the patient community, and derived from lessons learned from not only CMD-specific research and clinical programs, but also the experiences of those in other neuromuscular diseases, Cure CMD has developed the following subtype-specific research priorities.

Collagen 6 (Ullrich-Intermediate-Bethlem)
  • Pseudo-Exon Skipping. This type of gene therapy will “skip” the addition of an unwanted part of the gene to restore functionality.

  • Antisense. We all have two copies of each gene, often only one is affected (dominant mutations). This project aims to inhibit the faulty gene from expressing itself and allowing the unaffected gene to take over, restoring functionality.

  • Gene Replacement Therapy. Classical gene therapy approaches for recessive mutations.

  • Stop Codon Read-Through. A molecular intervention that uses compounds with the specific ability to mask the stop signal for protein synthesis as a consequence of a nonsense mutation (Ataluren in DMD is an example of this type of intervention).

  • Vectors Targeting COL6-Producing Cells. The main source of Collagen VI production are the fibroblast cells located in the muscle interstitial tissue, and gene therapy will need to target these cells. This project aims to discover, improve and/or “tune-up” this tool.

  • Understanding Contractures. The COL6 patient community has identified contractures as one of the progressive, incapacitating symptoms that most impact quality of life. We are focused on supporting research on contractures and identifying potential therapies to slow or even reverse this symptom.

αDG (Dystroglycanopathies)

In addition to the symptoms of muscle weakness, most forms of congenital dystroglycanopathy involve brain development defects which may express as cognitive impairment, seizures, or visual impairment. For affected individuals and their families, the search for solutions to manage the cognitive and neural complications of αDG is as important, if not more so, than muscle weakness.

  • Disease Model Development. For example, patient-induced pluripotent stem cells (iPSCs) can be converted into neural tissue or 3-D mini-brains, and transgenic mouse models, to help us understand the underlying mechanisms of brain development and allow for testing of potential interventions to boost neuronal plasticity and/or cognitive capacity.

  • Ribitol as a Potential Treatment. The addition of ribitol to αDG is necessary for its normal function. Some forms of αDG present a deficit in this step. Dietary administration of ribitol may be a promising therapy for some affected individuals, and we need to study this further.

  • Gene Therapy. Most genetic mutations that cause αDG could be amenable to some degree of correction by gene therapy.

  • Hinge-Like Project. One of the drivers of symptoms in two CMD subtypes (αDG and LAMA2) is the detachment of the basement membrane (part of the extracellular matrix) and the muscle plasma membrane.  This study aims to devise a “molecular hinge” to reconnect those two components bypassing the defect on the α-DG to restore function.

LAMA2 (Merosin Deficient/MDC1A)
  • LINKR Project. One of the drivers of symptoms in two CMD subtypes (LAMA2 and αDG) is the detachment of the basement membrane (part of the extracellular matrix) and the muscle plasma membrane. This study aims to reconnect those two components bypassing the absence or defect of the LAMA2 protein to restore function.

  • LAMININ 111 Protein Replacement Therapy. LAMA111 is the predominant laminin isoform in embryonic skeletal muscle but is replaced by LAMA211 after birth. LAMA111 and LAMA211 are structurally and functionally similar. This study aims to replace the affected LAMA211 production by reintroducing LAMA111. Researchers have successfully rescued the disease phenotype in mouse models, and the biotech company, Prothelia, in partnership with Cure CMD and LAMA2 experts, plans to move this potential therapy into human clinical trials.

  • Endogenous LAMA111 Overexpression. Similar to the previous priority, protein replacement of faulty LAMA211 by normal LAMA111 could be achieved by overexpressing the affected individual’s own production of LAMA111 by the use of a specific type of CRISPR approach. 

  • LAMA2 Natural History Study (NHS) in Children Ages 0-5 Years. Support the design and execution a two-part NHS to develop additional outcome measures and clinical trial endpoints in affected children ages 0-5 years.

LMNA (congenital laminopathies and related disorders)
  • Gene Therapy. LMNA-CMD is an autosomal dominant disorder, meaning that only one copy of the altered gene is enough to cause symptoms. The dominant-negative effect of the mutation makes gene therapy approaches a little more difficult, and therefore, support for studies to identify the best gene therapy tools for LMNA-CMD are critical.

  • Targeting LINC. Linkers of the Nucleoskeleton to Cytoskeleton, or “LINC” is a protein complex providing a structural link between the nucleus and the cytoplasm of muscle cells. Studies aimed at manipulating this complex have potential as a therapeutic target. 

  • Drug Profiling in DCM. A few small molecule drugs are currently in clinical trials for adults with LMNA-related dilated cardiomyopathy (DCM). Support for pre-clinical studies that move us closer to clinical trials for these interventions in the pediatric community will be pursued once proven safe and effective in adults.  

  • Natural History Study (NHS). Design and execute a prospective NHS based on data recently collected and published in a global retrospective study.

SELENON (SEPN1/RSMD)
  • Calcium Homeostasis Recovery and Oxidative Stress Reduction. The SELENON protein is likely involved in protecting muscle cells against oxidative stress, as well as playing a key role in the tight regulation of calcium storage and release needed for muscle contractions. As a result, mutations alter calcium homeostasis and triggers maladaptive cellular stress responses involving other proteins of the sarcoplasmic reticulum. Using cells from affected individuals and animal models, we aim to dissect this pathway with the potential to uncover novel therapeutic targets. 

  • Gene Therapy. The size of the components needed to deliver gene therapy treatments using classical AAV vectors may be larger than their cargo capacity. Moreover, function is mostly expressed during development, so it is an open question as to how effective gene therapy would be in affected adults. Therefore, additional support for studies aimed to overcome these roadblocks, and to find the most effective gene therapy approach are critical.

  • Disease-in-a-Dish Studies. This research aims to collect patient specimens such as fibroblasts (skin cells) to make patient-induced pluripotent stem cells (iPSCs) and then convert these cells into 3D muscle cells that can be used to screen thousands of potential interventions, as well as test gene therapy approaches.

  • Respiratory Natural History Data Collection. Collect data in a formal clinical study on respiratory function to both standardize respiratory care and identify outcome measures and clinical trial endpoints.

Questions?

 

Cure CMD continues to leverage knowledge, expertise, and the continually evolving priorities of the affected community, to move us closer to treatments for the congenital muscular dystrophies. Since 2008, we have elevated the status of CMD, from a low interest, low awareness, ultra-rare condition to a conspicuous group of genetic disorders, driving pharmaceutical interest and care optimization - all to fulfill our mission.

Have questions about Cure CMD’s Research Strategy? Please complete the form below and we'll be in touch!

CMD Research Inquiries

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