A large drawer of drugs that have fallen by the wayside due to their potent side effects, even if they prove their efficacy in the specific disease to be treated, could be reduced if dozens of ongoing studies in the field of photopharmacology bear fruit. As its name suggests, these drugs are activated by light only in the desired part of the body where they want to act and for a limited period of time.
Molecules in excess naturally bind to an array of light-sensitive chemicals. “They act like switches. They allow the drug to turn on and be active”, then turn it off when it’s back in the dark, explains Núria Camarero Palau, a researcher in the Nanoprobes and Nanoswitches group at the Institute of Bioengineering of Catalonia (IBEC).
When taking a traditional medicine, the compounds are released and distributed throughout the body, so “there is no way to control it,” says Amedu Leparia, head of the Medicinal Chemistry Group at the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC). . In photosensitive drugs, light acts as a “control element on pharmacological action,” although the researcher qualifies that light provides little benefit if traditional medicine is already effective. That’s why the focus is on drugs that “don’t work or don’t work well.”
On organs exposed to ambient light, such as the eye or skin, there is no need to use a specific device.
Photopharmacology is making rapid progress in diseases related to vision or skin, as these are areas that receive direct natural light, researchers said during a recent virtual discussion organized by the La Caixa Foundation. In addition, it enables advances in the study of neurotransmission, for example, with the aim of producing drugs that can act as inhibitors of neurons that acquire frenzied activity during seizures, explains Camarero. Both are participating in two initiatives, still in the early stages, for the development of photosynthetic drugs, which are financially supported by the project. CaixaResearch.
Spanish projects
Camarero is part of a project led by Dr. Pau Korostiza Langa on retinitis pigmentosa, a genetic disease that causes blindness. Its purpose is to restore vision by using the neural structures of the retina, making them sensitive and transmitting the ambient light signal to the brain. The first experiments in animal models (rodents) have had good results, so now they will look for eyes that are physiologically closer to humans, like pigs.
This solution is administered topically in the form of eye drops with a few drops in the eye. It activates the photoreceptors of neurons and the patient needs to be exposed only to natural light. The doctor notes that the drug can be tuned to a specific wavelength so that the molecule reacts to a specific light. In this case, white will suffice as it contains all the colors. “But it depends on the chemistry of the compound. We can also ‘tune’ the drug à la carte” so that it works based on different types of lighting.
This approach opens up a wide range of possibilities that they can explore in the future with more widespread pathologies, such as glaucoma, although the first step is to find a specific therapeutic target and then start designing and manufacturing the photoreceptor drug. .
The average time between development and coming to market can be 10 to 12 years
For its part, Leperia integrates Photoheart, a study focused on reducing heart lesions after a heart attack (cardiovascular disease is the leading cause of death in the Western world). Reperfusion performed for angioplasty saves the patient’s life, but causes death of cardiomyocytes (heart cells) in some areas due to metabolic shock. The medicine they create tries to restore them by controlling the ionic balance between sodium and calcium. But being in a dark area, it also requires a device to illuminate the area to make it work. And that’s where engineering comes in.
“This is, without exaggeration, a world-changing device,” said Pedro Irazocchi, professor of electrical and computer engineering at the Whiting School of Engineering at Johns Hopkins University (USA) and head of the team developing it. He agrees that it remains to be seen whether the molecule can be illuminated from the inside or the outside to avoid possible tissue damage, taking it to the site of action.
Transfer
For now, Irazoqui advances that a similar prototype has been successfully tested in mice while controlling the activity of a molecule to alter the perception of pain. The achievement represents “1%” of the “substantial” investment, he says, with the average cost to market being $200 million per device and $2,000 million per molecule.
Clinical use of these solutions “could take 10 to 12 years,” says Andrés G. Fernandez continues. Chief Scientific Officer Landsteiner Genmed, pending regulatory agencies’ approval, also includes a variable investment “not falling below several hundred million euros,” he adds.
On the other hand, the time frame for creating value may be too short to “allow for the entry of private capital into projects”. Achieving this will require certainty in patents, proof-of-concept drugs and devices, a driving group or the selection of “novel mechanisms of action” that provide therapeutic value compared to existing options. .
Medical tests
Camarero, a researcher at the Bioengineering Institute of Catalonia (IBEC), points out that the first clinical trials in the field of vision have already begun “for obvious reasons”, although he notes “very important advances” in development. of devices. Undoubtedly, one of the areas where they want to promote this type of medicine is oncology. “There are many research groups working to develop more effective drugs,” he points out.
As outlined by Johns Hopkins University (USA) professor Irazocki, the aim is to reduce the side effects of even treatments like chemotherapy. “If you have a chemo molecule that’s already approved for use in cancer, and you can modify it to act only inside the tumor, not outside, that would be chemotherapy without the side effects. That’s amazing.”
The future of photopharmacology, both scientists agree, is “promising.” As Leperia assesses, there is already a “basic science level” with evidence that these drugs work “better and differently” than conventional drugs. Both also mention the role of molecular biology in New Horizons. A particularly useful feature for diseases with “highly ineffective” treatments, he continues, “is to adjust drug response in almost real time.”
The industry follows closely and eagerly. In the case of Landsteiner Genmed, Fernandes admits they are “very attentive” to new ideas and products “emerging from public research” related to the cardiovascular dimension, where the company has its niche.
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