The Technion – Israel Institute of Technology has been Israel’s leading technological university for over a century and a global benchmark in applied research. Its influence has been instrumental in the development of Israel’s high-tech industry and in driving scientific advancements. As part of the DREAMS project, the Technion team, led by Associate Professor Shenhav Shemer, plays a critical role in the search for new therapies for five rare neuromuscular diseases. Their research focuses on identifying biomarkers and therapeutic targets, evaluating the effectiveness of novel molecules, and validating treatments in vivo and in vitro models, contributing significantly to medical progress in this field.
The DREAMS Project and Technion’s role
Leading Technion’s involvement in the DREAMS project is Associate Professor Shenhav Shemer, who heads a team with over a decade of experience in muscle research and related pathologies. Their expertise is central to the project, particularly in identifying molecular mechanisms that can be targeted therapeutically to treat muscle disease.
The Technion team plays a critical role in several key project areas: identifying biomarkers and therapeutic targets, evaluating the effectiveness of novel molecules designed to inhibit these targets to combat muscle diseases and validating these treatments in animal and cell models. These efforts are essential for advancing innovative therapies and deepening the understanding of the molecular and cellular mechanisms underlying rare neuromuscular diseases.
This work conducted by Technion’s team will be vital to the overall success of DREAMS. By focusing on biomarkers, therapeutic targets, and the evaluation of new drug candidates, this team’s research lays some of the groundwork necessary for developing effective treatments and deepening our understanding of the biological processes driving these conditions, a critical step in drug development.
Research on desmin: a key focus in the project
One of the Technion team’s key focuses in the DREAMS project is the study of desmin, a cytoskeletal protein vital to muscle structure. Through biochemical assays and advanced techniques such as high-resolution microscopy, the team investigates how desmin interacts with cell membranes, and whether it aggregates, which could indicate a disease.
Shemer’s lab is at the forefront of desmin intermediate filament (IF) research, having developed pioneering models that explain the breakdown and loss of these filaments in various types of muscle atrophy. Their deep expertise in the dynamics of desmin IFs, particularly their role in maintaining muscle structure and function, positions them to explore new therapeutic strategies.
“By targeting the mechanisms that disrupt desmin stability and function, we aim to develop drugs that prevent or reverse muscle deterioration in these disorders, preserving muscle function and slowing disease progression. This strategy not only provides a focused therapeutic target but also enhances our understanding of disease mechanisms, potentially uncovering new targets for intervention,” explains Professor Shemer.
Identifying biomarkers and developing therapies
The Technion team’s efforts are as well focused on identifying biomarkers that indicate muscle dysfunction, thereby facilitating the search for new treatments. This research will help identify potential “biomarkers” that signal muscle disorders, facilitating the discovery of new drugs for treating the neuromuscular diseases being studied in the DREAMS project.
“By identifying novel pathological defects and validating them as biomarkers, we not only provide valuable tools for drug selection within the DREAMS project, but also advance the broader scientific understanding of these rare disorders,” explains Professor Shemer.
Furthermore, the methodologies and models they are developing could likely be adopted by other researchers, amplifying the impact of their discoveries and facilitating progress toward effective solutions for rare diseases.
“Our work in characterizing the molecular mechanisms underlying neuromuscular diseases opens doors to new therapies that could extend beyond the five diseases DREAMS focuses on, potentially benefiting other conditions with similar pathological features,” Shemer explains, emphasizing the broader potential impact of the Technion initiative, which extends beyond the immediate goals of the DREAMS project.
Challenges and Strategies in Technion’s Research
The Technion team recognizes that working with rare neuromuscular diseases presents significant challenges, particularly due to the complexity and limited understanding of the underlying mechanisms. This makes it difficult to identify reliable biomarkers or therapeutic targets. To address these obstacles, they plan to integrate multiple advanced tools, including multi-omics approaches and in vivo models, along with advanced biochemical assays and high-resolution microscopy. By integrating diverse data sources, they aim to uncover new insights into disease pathways, ultimately improving their ability to pinpoint actionable biomarkers and therapeutic targets.
Another challenge is the significant variability in how these diseases manifest across different patients, complicating biomarker validation. To overcome this, the team will tailor their drug screening and validation processes to specific patient subgroups, increasing the likelihood of effective therapies. Collaboration with DREAMS clinical partners to access diverse patient samples will further ensure that their findings are broadly applicable.
A final challenge lies in translating results from cultured cells and animal models to human patients due to species-specific differences in disease pathology and drug response. To mitigate this, the team will focus on human-derived iPSC cells differentiated into muscle cells, comparing them with murine study samples. This approach will allow for validation in a human context before progressing to clinical trials.
