DM1-Hub

The DM1-Hub project outlines a unique proposal aimed at improving the quality of life of DM1 patients by generating unprecedented clinical, (epi)genetic, and proteomic data through the creation of a registry of 3,000 DM1 patients and the use of state-of-the-art long-read sequencing and proteomics technologies. The comprehensive analysis of these data will expand our understanding of the progression of this rare disease and enable more precise application of therapies that are expected to be approved in the near future.

As mentioned previously, despite being a rare disease, DM1 has a relatively high and heterogeneous prevalence, with an estimated population in Spain of 5,000–10,000 patients and around 100,000 people in Europe, making it the most common adult muscular dystrophy. DM1 is a genetic disorder that is transmitted with a 50% probability to offspring, and its symptoms can manifest at any stage of life, from birth to old age. It is a multisystemic disease affecting multiple organs, including muscle, the CNS, the cardiovascular, respiratory, and gastrointestinal systems, with different degrees of involvement among patients. However, the clinical, genetic, and molecular factors underlying this phenotypic variability are not well understood, making it difficult to implement personalized preventive medicine strategies for each patient. Importantly, DM1 patients have a reduced life expectancy compared to healthy individuals, mainly due to cardiovascular and respiratory involvement. In addition, the onset of disabilities associated with central nervous system dysfunction is highly relevant, yet their underlying mechanisms remain poorly understood.

Although this disease has established diagnostic and follow-up protocols, and there are some palliative treatments that alleviate certain symptoms, there are still many open clinical questions related to diagnosis (what is the patient’s clinical form? is it possible to prevent or delay symptoms?), disease monitoring (what will its progression be? which organs will be affected?), and treatment (which patients will respond better or worse to a given drug? when is the optimal time to initiate therapy?). Moreover, there is no natural history study of DM1 in Spain to provide data that could facilitate these processes. For all these reasons, healthcare professionals currently lack tools to support these decisions, and therefore the execution of this project will be essential to strengthen the capacity of the Spanish National Health System in managing this disease.

The DM1-Hub project aims, through the study of patients and blood samples in the first sizeable cohort of its kind, to identify predictors that help answer these questions. This will allow, among other things, the anticipation of severe specific clinical phenotypes—such as cardiac or respiratory complications—in asymptomatic patients, or the stratification of the DM1 population into subgroups to identify, with objective criteria, those patients most likely to respond to a specific pharmacological treatment. Thus, clinical, (epi)genetic, and proteomic data will become powerful tools for monitoring DM1, available to healthcare professionals and directly improving quality of life—and even survival—of many patients with this condition. Quantitatively, this will also reduce healthcare costs associated with patient monitoring and optimal treatment (details extensively described in the relevance and applicability section). Finally, it should be emphasized that the data and conclusions generated can be extrapolated to other DM1 populations and compared with similar studies conducted in other countries.

The success of this project would make it possible to propose the integration of third-generation sequencing technologies and biomarker detection into healthcare systems, approaches that could also be extended to other repeat-expansion diseases.

Qué es DM1-Hub