Periodic Reporting for period 1 - MiRepair (MiRNAs as therapeutics for neurorepair in Multiple Sclerosis)
Reporting period: 2021-06-01 to 2023-05-31
Multiple sclerosis (MS) is a chronic complex neurological disease of the central nervous system (CNS), which affects 2.3 million people worldwide. One of the main pathological characteristics of multiple sclerosis is demyelination, which involves the injury and loss of myelin sheaths. Myelin is a material that surrounds the part of the neurons that transmit electric impulses from one neuron to the next one (axons). When myelin is intact, axons are insulated, and the electric impulses are transmitted efficiently. However, during demyelination, myelin is damaged, and these nerve impulses are slowed down causing different symptoms in the patients. There is a natural process in the brain, called remyelination, that can partly or completely repair these demyelinated lesions. However, this process is often disrupted in multiple sclerosis patients.
The cause of MS is still unknown, but it has been proposed that some genetic and environmental factors are related to MS pathology. microRNAs (miRNAs) are involved in the interaction between these genetic and environmental factors. miRNAs are molecules that can regulate the expression of different genes and have been found altered in several diseases. Specifically in MS, miRNAs have been found to be dysregulated in different tissues and biological fluids.
All current disease-modifying therapies in MS are unable to prevent the progressive accumulation of disability and to induce the endogenous repair of the brain. Thus, it is critical that innovative therapeutics that can promote remyelination are designed to address this deficit to treat MS patients. The main research goal of MiRepair project was to identify potential miRNAs related to demyelination and remyelination and to study their therapeutic potential to enhance remyelination in MS.
The findings of the project suggests that a specific miRNA and its target genes are potential candidates to enhance remyelination, neurorepair and reduce neuroinflammation in MS.
The cause of MS is still unknown, but it has been proposed that some genetic and environmental factors are related to MS pathology. microRNAs (miRNAs) are involved in the interaction between these genetic and environmental factors. miRNAs are molecules that can regulate the expression of different genes and have been found altered in several diseases. Specifically in MS, miRNAs have been found to be dysregulated in different tissues and biological fluids.
All current disease-modifying therapies in MS are unable to prevent the progressive accumulation of disability and to induce the endogenous repair of the brain. Thus, it is critical that innovative therapeutics that can promote remyelination are designed to address this deficit to treat MS patients. The main research goal of MiRepair project was to identify potential miRNAs related to demyelination and remyelination and to study their therapeutic potential to enhance remyelination in MS.
The findings of the project suggests that a specific miRNA and its target genes are potential candidates to enhance remyelination, neurorepair and reduce neuroinflammation in MS.
To decipher the role of microRNAs (miRNAs) in demyelination and remyelination, OpenArray panels were used to profile specific miRNA signatures during demyelination and remyelination. These panels have been designed to allow the identification of 215 miRNAs. Brain slices obtained from mice were used and treated to induce demyelination, as observed in multiple sclerosis (MS) patients. Afterwards, these brain slices also presented remyelination. Thus, a comparative analysis between miRNA profiles in this experimental model of demyelination and clinical samples from MS patients was carried out to select a potential miRNA involved in the processes. Moreover, individual cells from these brain slices were isolated and how genes were expressed in each individual cell was analyzed. Specific gene signatures during demyelination and remyelination for each cell type in the brain were obtained.
To explore miRNA modulation as a potential therapeutic for harnessing remyelination, an in vitro model of neuroinflammation was established. The potential effect of miRNA inhibition on the specific cells in the brain that are able to produce new myelin sheaths around the axons was explored to study remyelination potential. Collectively, the findings of the MiRepair project suggests that a specific miRNA and its target genes are potential candidates to enhance remyelination, neurorepair and reduce neuroinflammation in MS.
The main results of the project have been presented at national and international level and one manuscript is in progress and estimated to be ready for publication in August.
To explore miRNA modulation as a potential therapeutic for harnessing remyelination, an in vitro model of neuroinflammation was established. The potential effect of miRNA inhibition on the specific cells in the brain that are able to produce new myelin sheaths around the axons was explored to study remyelination potential. Collectively, the findings of the MiRepair project suggests that a specific miRNA and its target genes are potential candidates to enhance remyelination, neurorepair and reduce neuroinflammation in MS.
The main results of the project have been presented at national and international level and one manuscript is in progress and estimated to be ready for publication in August.
Multiple sclerosis (MS) is clinically heterogenous. Most individuals are diagnosed with a subtype associated to an inflammatory burden. For that reason, they can benefit from using most of the current therapeutic options as they modulate this inflammatory response. However, there are really few therapeutic options for those subjects with progressive MS forms. These progressive forms affect more than 1 million individuals globally. Although some molecules have been studied for their neuroprotective properties, there is still knowledge gaps concerning remyelination. MiRepair project has exploited that and has proposed a new potential remyelinating strategy to be used in all forms of MS.