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
Hidden Scars: How COVID Lockdowns Altered Teen Brains Forever
Research from the University of Washington revealed that COVID-19 lockdowns led to accelerated cortical thinning in adolescents, impacting brain development significantly. This effect was more pronounced in females than males, raising concerns about long-term brain health. The study [...]
Simple Blood Test To Detect Dementia Before Symptoms Appear
UCLA researchers have identified placental growth factor (PlGF) as a potential blood biomarker for early detection of cognitive impairment and dementia. High PlGF levels correlate with increased vascular permeability, suggesting its role in the development [...]
Investing Goldman Sachs asks ‘Is curing patients a sustainable business model?’
Goldman Sachs analysts attempted to address a touchy subject for biotech companies, especially those involved in the pioneering “gene therapy” treatment: cures could be bad for business in the long run. “Is curing patients [...]
The risks of reversed chirality: Study highlights dangers of mirror organisms
A groundbreaking study evaluates the feasibility, risks, and ethical considerations of creating mirror bacteria with reversed chirality, highlighting potential threats to health and ecosystems. In a recent study published in Science, a team of researchers [...]
Alarming Mutation in H5N1 Virus Raises Pandemic Red Flags
NIH-funded study concludes that the risk of human infection remains low A recent study published in Science and funded by the National Institutes of Health (NIH) has found that a single alteration in a protein on the surface [...]
Scientists Discover Genetic Changes Linked to Autism, Schizophrenia
The Tbx1 gene influences brain volume and social behavior in autism and schizophrenia, with its deficiency linked to amygdala shrinkage and impaired social incentive evaluation. A study published in Molecular Psychiatry has linked changes in brain [...]
How much permafrost will melt this century, and where will its carbon go?
Among the many things global warming will be melting this century—sea ice, land glaciers and tourist businesses in seaside towns across the world—is permafrost. Lying underneath 15% of the northern hemisphere, permafrost consists of [...]
A Physics Discovery So Strange It’s Changing Quantum Theory
MIT physicists surprised to discover electrons in pentalayer graphene can exhibit fractional charge. New theoretical research from MIT physicists explains how it could work, suggesting that electron interactions in confined two-dimensional spaces lead to novel quantum states, [...]
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 [...]
