05/12/2024
With Light Against Inner Darkness
Millions of people worldwide suffer from depression. When medications fail, Syntropic Medical’s 60-hertz light therapy could offer new hope.
By Larissa Tetsch
Psychiatric illnesses are not only a burden for those affected and those around them, but also for the health and social systems due to high treatment costs and loss of work time. Depression in particular is common, with more than 300 million sufferers worldwide, 90 million of whom are in Europe. Despite intensive research, most therapies are still based on pharmacological active ingredients that have essentially been known for 50 years. If these do not work or the side effects are unacceptable for those affected, there are hardly any other treatment options. Syntropic Medical GmbH , a spin-off of the Institute of Science and Technology Austria (ISTA) in Klosterneuburg, Lower Austria, is therefore working on a non-pharmacological and non-invasive therapy option that uses flickering light. One of the founders is the neurobiologist Sandra Siegert , who, as a professor at the ISTA, researches the function of microglia in the brain and their interaction with nerve cells.
Fixed synapses
Microglia cells are the macrophages of the brain, i.e. immune cells that are specialized in monitoring their environment and neutralizing infectious agents and degenerated or infected cells through phagocytosis. In addition, they can influence both neuronal circuits and the restructuring of the extracellular matrix. They therefore have a major influence on the brain’s ability to adapt flexibly to new situations and environmental influences – a property known as plasticity. The latter is typically very high in young brains and decreases with increasing age, which ultimately explains why younger people generally find it easier to learn than older people.
At the cellular level, plasticity is limited by components of the extracellular matrix that form perineural networks around nerve cells and synapses, thereby stabilizing existing connections on the one hand, but also making it more difficult to form new synapses on the other. Memories are thus consolidated and new experiences are difficult to store. The path to a rejuvenated brain that is capable of learning again seems clear: targeted dissolution of the perineural networks should give the brain back its plasticity. In fact, intensive research is being carried out on this.
Surprising anesthetic effect
At the ISTA, Siegert and her colleague Alessandro Venturino discovered a new way to dissolve perineural networks quite by chance. “For a study, we compared two different anesthetics,” recalls the neuroscientist. “One of them was ketamine, which is often used in anesthesia and, interestingly, is also used to treat depression when other therapies fail.” The researchers were surprised to find that repeated anesthesia with ketamine activated the microglia. And that was not all, as Siegert explains: “Further studies showed us that the activated microglia break down the perineural networks around the synapses. That was a very unexpected result for us.”
As microglia researchers, Siegert and Venturino naturally wanted to understand how ketamine affects the microglia. Electroencephalograms showed that ketamine triggers so-called gamma waves in the brain, i.e. brain waves with an oscillation in the 60-hertz range. Gamma waves naturally occur with increased attention, concentration and learning processes. Once it was clear that these waves activate the microglia, the researchers had an idea: “We wanted to investigate whether we could achieve the same effect if we replicated the waves by sending light with a frequency of 60 hertz through the eyes into the brain,” says Siegert.
Window for interventions
The approach worked, and as expected, the activated microglia began to break down the perineural networks. Since no side effects occurred, the idea of light therapy was born. “With light therapy, we can break up the networks and enable the formation of new synapses. And this is limited to a certain time window: when the treatment is stopped, the networks form again,” Siegert summarizes. “This gives us a therapeutic window for interventions with which we can bring about changes that will hopefully be permanent.”
In order to develop a therapy based on these research results, however, Siegert and Venturino needed partners outside of the academic environment. In short, a company had to be founded. Fortunately, the ISTA places great value on technology transfer and explicitly supports it with its subsidiary xista innovation (more about Austria as a start-up location in our 2-part series “In and around Vienna” here and here ). Siegert was also open to the idea of a spin-off. “The Tech Transfer Office here at ISTA was enthusiastic about our idea and supported us with intellectual property,” recalls the company founder. Then Covid came and put the brakes on the project for the time being. “That gave us time to put together a founding team,” says Siegert looking back.
Founded after the pandemic
The company was officially founded in 2023; today nine people work for Syntropic Medical, including the four-person founding team of Sandra Siegert, Alessandro Venturino, Mark Caffrey as CEO and Jack O’Keeffe as CTO. Siegert and Venturino continue their scientific work at the ISTA and also support the new company: while Siegert primarily has an advisory role, Venturino, as Head of Research, is responsible for the development of new technological applications. Financing is currently provided by the venture capital fund xista science ventures , which is partly owned by the ISTA, and Austria Wirtschaftsservice Gesellschaft GmbH (AWS). The venture fund supports scientific start-ups, including those from the life sciences, in the early stages of their founding, while AWS is a development bank of the Austrian State.
Finding a suitable name for the new company, however, was somewhat difficult. The obvious choice would be “light” as part of the name, but the founders decided against it because the English word “light” is already used by many companies. In their search for a unique selling point, they came up with “synapse”, which was linked to the term “tropism” (ancient Greek for “turn”). Just as tropism describes a directed growth in response to an external stimulus, light therapy is supposed to make new synapses grow.
Therapy glasses in development
At the moment, the start-up is concentrating on using light therapy to treat depression that has so far been resistant to treatment. The aim is to develop a medical device that can be worn like glasses. Syntropic Medical has already demonstrated in a pilot study with volunteers that the flickering light can be brought into the brain in this way. A first clinical phase 2 study with patients is due to begin next year. Another possible application is also to be tested in an ERC-funded proof-of-concept study , as Siegert explains: “We want to check whether our light therapy is also suitable for the treatment of post-traumatic stress disorder (PTSD).”
Since PTSD is caused by traumatic memories becoming more and more entrenched, light therapy seems to be predestined for its treatment – in the time window with increased brain plasticity, stressful memories could be specifically overwritten by new positive experiences. Further studies will have to show whether this works. Ultimately, the Syntropic founder and her colleagues hope that their medical device will enable the treatment of neuropsychiatric illnesses directly in the comfort of patients’ homes. “Depression and PTSD are still a stigma for many people,” says Siegert. “Treatment at home would certainly be a relief for them.”
Larissa Tetsch
Image: Pixabay/JillWellington