A team of researchers from the Institute for Bioengineering of Catalonia (IBEC) has developed light-activated derivatives of the anti-epileptic drug carbamazepine to treat neuropathic pain.
Light can be harnessed to target drugs to specific body areas using photopharmacology. This technique modifies the drug’s chemical structure by incorporating a light-sensitive molecular switch, like azobenzene. As a result, the drug becomes active only under exposure to certain light wavelengths, remaining inactive in the dark.
Based on these principles, a team of researchers led by the Institute for Bioengineering of Catalonia (IBEC) has developed photoswitchable derivatives of carbamazepine, an anti-epileptic drug widely used in medicine to combat some types of neuropathic pain, such as trigeminal neuralgia. These compounds, which have an analgesic effect when activated by light, are able to inhibit nerve signals locally and on demand. The derivatives synthesized by the researchers are activated at wavelengths corresponding to the amber color, which allows them to pass through tissue and bone using conventional halogen lamps.
The two synthesized compounds, carbazopine-1, and carbadiazocine, show photopharmacological activity, allowing the activity of hippocampal neurons and the locomotion of zebrafish larvae to be reversibly controlled by light. These in vivo experiments make it possible to observe anxiety-related behaviors reflected in sudden swimming movements. IBEC researcher Luisa Camerin, the first author of the study, explains: “When we illuminate larvae that have uptaken these compounds with a certain wavelength, the drug is activated and the larvae move faster. If we change the wavelength, their movement slows down again, demonstrating the reversible effect of the compound on the nervous system.
Pain Management Innovations
Carbadiazocine has also been shown to have analgesic properties: “In rat models developed in the laboratory of Esther Berrocoso at the University of Cadiz, we have observed that carbadiazocine has an analgesic effect on neuropathic pain without any signs of anesthesia, sedation or toxicity. These results demonstrate a simple and convincing treatment with non-invasive illumination,” explains Pau Gorostiza, ICREA research professor, principal investigator at IBEC, and member of CIBER-BBN.
Zebrafish larvae. Credit: Institute for Bioengineering of Catalonia (IBEC)
Neuropathic pain is caused by lesions or diseases of the somatosensory system, such as lumbar radiculopathy (“sciatica”), diabetic neuropathy, and chronic post-operative pain. The treatment of this type of pain often requires opioids, which are stronger analgesics than the usual NSAIDs – such as paracetamol and ibuprofen. However, their use is controversial due to their inconsistent efficacy, the need for high doses that can lead to tolerance and addiction, and systemic side effects such as constipation, nausea, dizziness, and drowsiness.
In this context, light-based therapies are becoming increasingly important in medicine because of their ability to target specific regions of the body, increasing treatment efficacy and reducing the side effects of systemic drugs.
The team is already working on the next step in this project, which will involve activating drugs using infrared light, which penetrates deeper into tissue, and using portable light sources such as lasers or light-emitting diodes (LEDs).
Reference: “Photoswitchable carbamazepine analogs for non-invasive neuroinhibition in vivo” by Luisa Camerin, Galyna Maleeva, Alexandre Gomila-Juaneda, Irene Suárez-Pereira, Carlo Matera, Davia Prischich, Ekin Opar, Fabio Riefolo, Esther Berrocoso and Pau Gorostiza, 18 June 2024, Angewandte Chemie International Edition.
DOI: 10.1002/anie.202403636
This study is part of the PHOTOTHERAPORT project, coordinated by the Institute for Bioengineering of Catalonia (IBEC). The project is funded by the prestigious Pathfinder Open program of the European Innovation Council (EIC) and focuses on the development of luminescent implants and light-activated drugs for innovative neuromodulation therapies (HORIZON-EIC-2023 program PATHFINDEROPEN-01, no. 101130883). PHOTOTHERAPORT is a consortium of 8 institutions from 4 countries with a budget of 3 million euros over 3 years to carry out the project.
News
Inside the Nano-Universe: New 3D X-Ray Imaging Transforms Material Science
A cutting-edge X-ray method reveals the 3D orientation of nanoscale material structures, offering fresh insights into their functionality. Researchers at the Swiss Light Source (SLS) have developed a groundbreaking technique called X-ray linear dichroic orientation tomography [...]
X-chromosome study reveals hidden genetic links to Alzheimer’s disease
Despite decades of research, the X-chromosome’s impact on Alzheimer’s was largely ignored until now. Explore how seven newly discovered genetic loci could revolutionize our understanding of the disease. Conventional investigations of the genetic contributors [...]
The Unresolved Puzzle of Long COVID: 30% of Young People Still Suffer After Two Years
A UCL study found that 70% of young people with long Covid recovered within 24 months, but recovery was less likely among older teenagers, females, and those from deprived backgrounds. Researchers emphasized the need [...]
Needle-Free: New Nano-Vaccine Effective Against All COVID-19 Variants
A new nano-vaccine developed by TAU and the University of Lisbon offers a needle-free, room-temperature-storable solution against COVID-19, targeting all key variants effectively. Professor Ronit Satchi-Fainaro’s lab at Tel Aviv University’s Faculty of Medical and [...]
Photoacoustic PDA-ICG Nanoprobe for Detecting Senescent Cells in Cancer
A study in Scientific Reports evaluated a photoacoustic polydopamine-indocyanine green (PDA-ICG) nanoprobe for detecting senescent cells. Senescent cells play a role in tumor progression and therapeutic resistance, with potential adverse effects such as inflammation and tissue [...]
How Dysregulated Cell Signaling Causes Disease
Cell signaling is crucial for cells to communicate and function correctly. Disruptions in these pathways, caused by genetic mutations or environmental factors, can lead to uncontrolled cell growth, improper immune responses, or errors in [...]
Scientists Develop Super-Strong, Eco-Friendly Plastic That Bacteria Can Eat
Researchers at the Weizmann Institute have developed a biodegradable composite material that could play a significant role in addressing the global plastic waste crisis. Billions of tons of plastic waste clutter our planet. Most [...]
Building a “Google Maps” for Biology: Human Cell Atlas Revolutionizes Medicine
New research from the Human Cell Atlas offers insights into cell development, disease mechanisms, and genetic influences, enhancing our understanding of human biology and health. The Human Cell Atlas (HCA) consortium has made significant [...]
Bioeconomic Potential: Scientists Just Found 140 Reasons to Love Spider Venom
Researchers at the LOEWE Centre for Translational Biodiversity Genomics (TBG) have discovered a significant diversity of enzymes in spider venom, previously overshadowed by the focus on neurotoxins. These enzymes, found across 140 different families, [...]
Quantum Algorithms and the Future of Precision Medicine
Precision medicine is reshaping healthcare by tailoring treatments to individual patients based on their unique genetic, environmental, and lifestyle factors. At the forefront of this revolution, the integration of quantum computing and machine learning [...]
Scientists Have Discovered a Simple Supplement That Causes Prostate Cancer Cells To Self-Destruct
Menadione, a vitamin K precursor, shows promise in slowing prostate cancer in mice by disrupting cancer cell survival processes, with potential applications for human treatment and myotubular myopathy therapy. Prostate cancer is a quiet [...]
Scientists reveal structural link for initiation of protein synthesis in bacteria
Within a cell, DNA carries the genetic code for building proteins. To build proteins, the cell makes a copy of DNA, called mRNA. Then, another molecule called a ribosome reads the mRNA, translating it [...]
Vaping Isn’t Safe: Scientists Uncover Alarming Vascular Risks
Smoking and vaping impair vascular function, even without nicotine, with the most significant effects seen in nicotine-containing e-cigarettes. Researchers recommend avoiding both for better health. Researchers have discovered immediate impacts of cigarette and e-cigarette [...]
Twice-Yearly Lenacapavir for PrEP Reduces HIV Infections by 96%
Twice-yearly injections of the capsid inhibitor drug lenacapavir can prevent the vast majority of HIV infections, according to a Phase 3 clinical trial published Wednesday in the New England Journal of Medicine. HIV pre-exposure [...]
Did Social Distancing Begin 6,000 Years Ago? Neolithic Villagers May Have Invented It
Social distancing may have roots 6,000 years ago, as research shows Neolithic villages like Nebelivka used clustered layouts to control disease spread. The phrase “social distancing” became widely recognized in recent years as people [...]
Decoding Alzheimer’s: The Arctic Mutation’s Role in Unusual Brain Structures
Researchers have uncovered how certain genetic mutations lead to unique spherical amyloid plaques in inherited forms of Alzheimer’s, offering insights that could advance our understanding of the disease and improve therapeutic strategies. An international collaboration [...]
