Molecular Aspects of Mucopolysaccharidoses

Mucopolysaccharidoses (MPS) is a group of 11 diseases belonging to lysosomal storage disorders (LSD), which occur with cumulative frequencies of all their types of about 1 per 40,000 – 50,000 live births. These diseases are caused by mutations in genes coding for enzymes involved in the degradation of glycosaminoglycans (GAGs) (formerly called mucopolysaccharides). Their impaired hydrolysis leads to continuous accumulation and storage of these compounds in the cells of patients, which results in damage to the affected tissues, including the heart, respiratory system, bones, joints, and central nervous system. MPS are usually fatal diseases (especially neuronopathic forms of MPS), with an average expected life-span of one or two decades. MPS are monogenic diseases, which are often considered model genetic diseases in studies on the mechanisms of genetic disorders and the development of novel therapeutic strategies.

Although MPS are monogenic diseases, recent studies demonstrated that their pathology is significantly more complex than the primary effects of GAG storage on lysosomal function. It appeared that the expression of hundreds of genes is changed in MPS cells and many cellular processes are significantly affected. This causes further changes in the function of tissues, organs, and the whole body. Nevertheless, our knowledge of molecular processes occurring in MPS cells, and disease-specific changes relative to normal cells, is very limited. On the other hand, understanding the molecular pathology of the disease, especially molecular aspects of various interactions between biologically active macromolecules, is crucial for both gaining basic knowledge on the regulation of various biological processes and developing new therapeutical strategies for genetic diseases which are particularly difficult to cure. In fact, previous studies on MPS allowed us to achieve spectacular progress in understanding principles of various genetic disorders and to propose many sophisticated therapeutical options, including enzyme replacement therapy, substrate reduction therapy, modifications of gene therapies, and many others. Therefore, this special issue is devoted to increasing our knowledge on molecular aspects of MPS which should have a significantly broader meaning for biomedical sciences. 

The scope of this Research Topic is to publish papers contributing significantly to understand molecular aspects of MPS. Specific aims include, but are not restricted to: 

• Macromolecular interactions in MPS cells 

• Changes in gene expression regulation

• Cellular processes affected in MPS cells

• Novel therapeutic approaches based on molecular mechanisms of MPS 

• Improved diagnostic methods for detection of MPS

• Genotype-phenotype correlations  

• New attempt for accurate prediction of disease course, based on molecular studies

Various types of papers will be considered, including original reports and review articles. Papers presenting laboratory studies on cellular and animal models are welcome, as are manuscripts describing works conducted with patients and patient-derived biological materials.

Prof. Luigi Michele Pavone holds an Italian patent titled "Compositions for the therapy of mucopolysaccharidoses". Prof. Pavone declares no additional competing financial interests. All other co-editors declare no conflicts of interest.