Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects motor neurons and the spinal cord, causing loss of muscle control and ultimately death. In Spain it is the third most widespread neurodegenerative disease, after Alzheimer’s and Parkinson’s, and today there is no cure. Despite research advances, current treatments only slightly slow disease progression, underscoring the urgent need to develop new therapeutic approaches.
Iker Belintxon, graduate of the Faculty of Chemistry of the University of the Basque Country (UPV/EHU), developed his final graduation project in the research group “Sustainable Catalysis: Methods and Calculation” of the UPV/EHU, in collaboration with the Neuromuscular Disease Research Group of the BioGipuzkoa Health Institute. This collaboration, which brings together experts from different disciplines, aims at research on ALS in the strategic area IKUR-2030, sponsored by the Basque Government (NEURODEGENPROT Project).
“In BioGipuzkoa,” explains Iker Belintxon, “the existence of a relationship between the degeneration of motor neurons and the imbalance in the concentration of very long-chain fatty acids in the organism was recently discovered. Abnormally high concentrations of some very long-chain fatty acids have been observed in ALS patients, the biosynthesis of which is carried out by enzymes called elongases (ELOVLs) that add two carbon atoms to a carboxylic acid chain.
In his study, Iker Belintxon focused on the ELOVL6 elongase. “We saw that the ELOVL6 elongase can be very interesting, as it regulates other types of ELOVL.” For the design of new compounds, previously known inhibitors of the said enzyme (substances that block the action of enzymes) were taken into consideration. “After examining the inhibitors, we identified several limitations, such as difficulty dissolving in water and complex structures. For this reason, we decided to design and synthesize new molecules.”
Iker Belintxon in front of the UPV/EHU Chemistry Faculty. (Photo: Jorge Navarro / UPV/EHU Communications Office)
The new regulators have been designed with improved properties. “These molecules avoid the above problems, such as complex structure, and have good pharmacological properties when administered orally. This is essential for the drug to be effective in the body, as the pharmacokinetics of a drug determine the appearance, duration and intensity of its effects.”
To design the new compounds, “computational calculations called ‘docking’ were carried out to predict how the new molecules interact with the enzyme. Once the best results were selected, they were plotted in a visualizer to structurally detail these interactions and observe how the molecules couple with the enzyme. “These programs provide information to identify which parts of the molecules are most important for their function.”
To finish the work, after carrying out this analysis in detail, Iker synthesized the molecules that showed the best results. “These new compounds were sent to BioGipuzkoa to carry out clinical trials and evaluate their efficacy. I would also like to underline that this work represents the first approach to a completely new project, which could open new avenues in the fight against ALS,” he concludes.
Iker Belintxon Lizarazu achieved top marks in his graduation project entitled “Design and synthesis of new ELOVL6 elongase regulators for the treatment of amyotrophic lateral sclerosis (ALS)”, carried out under the direction of professors Maialen Sagartzazu and Jesús María Aizpurua at the Faculty of Chemistry of the UPV/EHU. He is currently studying a Master’s degree in Synthetic and Industrial Chemistry at the Basque Public University. (Source: UPV/EHU)
What are the latest breakthroughs in ALS research that Iker Belintxon is exploring?
Time.news Interview: Exploring Breakthroughs in ALS Research with Iker Belintxon
Editor: Welcome to Time.news! Today, we’re diving into an important topic: Amyotrophic Lateral Sclerosis (ALS). With us is Iker Belintxon, a graduate from the University of the Basque Country and a key contributor to innovative ALS research. Iker, thank you for joining us!
Iker Belintxon: Thank you for having me! It’s a pleasure to discuss our work on such a critical issue.
Editor: To start, could you give our readers a brief overview of what ALS is and its impact?
Iker Belintxon: Absolutely. ALS is a devastating neurodegenerative disease that specifically affects motor neurons in the brain and spinal cord. This leads to progressive muscle weakness, loss of motor function, and, unfortunately, death. In Spain, it’s the third most prevalent neurodegenerative disease after Alzheimer’s and Parkinson’s. Currently, there is no cure, and available treatments only slow disease progression marginally. This makes our research even more vital as we look for new therapeutic approaches.
Editor: That’s sobering. I understand you’ve been researching the role of very long-chain fatty acids and an enzyme known as ELOVL6 in ALS. Can you explain how that came about?
Iker Belintxon: Certainly! Our research began with a collaboration between the Sustainable Catalysis research group at my university and the Neuromuscular Disease Research Group at BioGipuzkoa. We discovered a relationship between motor neuron degeneration and an imbalance of very long-chain fatty acids in ALS patients. Elevated levels of these fatty acids are linked to the functionality of an enzyme called elongase, specifically ELOVL6, which is responsible for their biosynthesis.
Editor: That’s fascinating! How does ELOVL6 specifically factor into the progression of ALS?
Iker Belintxon: ELOVL6 is particularly interesting because it regulates other elongases that contribute to these fatty acid profiles. We hypothesized that by targeting ELOVL6 with newly designed molecules, we could influence the fatty acid levels and potentially alter the disease’s progression.
Editor: You mentioned designing new compounds to regulate ELOVL6. What sets these compounds apart from previous inhibitors that were studied?
Iker Belintxon: Great question! Previous inhibitors faced significant limitations, like poor solubility in water and overly complex structures, which made them less effective. We focused on creating new molecules that bypass these issues, simplifying the structures and improving their properties for better efficacy.
Editor: That’s quite an endeavor! What are the next steps for you and your team in this research?
Iker Belintxon: The next steps involve rigorous testing of these new compounds to assess their effectiveness in altering the fatty acid levels and their overall impact on motor neuron survival. We hope to contribute significantly to the existing knowledge and treatment options for ALS.
Editor: It sounds like your research holds enormous promise. What message would you like to share with those affected by ALS and their families?
Iker Belintxon: I want to emphasize that while there is currently no cure, researchers around the world are tirelessly working to find new solutions. It’s crucial for patients and families to stay hopeful and informed. Advocacy and support for research initiatives can make a significant difference in advancing our understanding and treatment of ALS.
Editor: Thank you, Iker, for your insights and dedication to this critical research. We wish you and your team the best of luck as you continue this essential work.
Iker Belintxon: Thank you! I appreciate the opportunity to share our findings. Together, we can make strides toward better outcomes for those affected by ALS.
Editor: Thank you to our readers for joining us in this vital conversation. Stay tuned for more updates on groundbreaking research in neurodegenerative diseases!
