Laser focus on neurodegenerative disease
Millions of people across Europe live with the effects of neurodegenerative diseases like Alzheimer’s and Huntington’s, and the numbers are set to rise further in the coming years. We spoke to Professor Edik Rafailov about the work of the NEUROPA project in developing a new method of treating neurodegenerative disease, based on the emerging field of phytoptogenetics.
There is currently no cure for neurodegenerative diseases like Alzheimer’s and Huntington’s disease, so treatment is typically focused on managing and mitigating the symptoms. Now researchers in the EUfunded NEUROPA project are exploring a potential new approach to treating these diseases, based on ideas from the field of optogenetics. “The main ultimate aim in the project is to treat diseases like Alzheimer’s and Parkinson’s in a non-invasive way,” says Edik Rafailov, coordinator of NEUROPA project and Professor in the Aston Institute of Photonics Technology at Aston University. Globally, researchers are exploring the potential of optogenetics techniques, involving the use of light to effectively control cells, as a means to stimulate certain parts of the brain. “A type of protein called opsins are known to detect light. These opsins can be placed in biological tissue and illuminated, then it’s possible to activate or inhibit certain cells,” explains Professor Rafailov.
Laser source
The problem in terms of treating neurodegenerative diseases is that while these opsins can be activated by visible light, this wavelength cannot be transmitted through the skull. Professor Rafailov has taken
up the challenge of developing a compact ultra-short pulse laser source in near-IR wavelength range to non-linearly activate phytochromes, a type of photoreceptor that is found in plants, opening up a new field of research called phytoptogenetics. This wavelength range enables researchers to perform this activation non-invasively through the skull. “We are trying to activate phytochrome switches in a nonlinear way. We can activate these phytochromes with
This delivery of ultra-short pulses can be used to activate phytochromes using nonlinear phenomenon located close to the surface of the brain. The phytochromes are also delivered into the brain non-invasively via AAV (Adeno Associated Virus) viruses which are administered intra-nasally. “Our partners in the project have developed these AAV viruses using directed evolution methods, and phytochromes will be placed on them. Through this approach
he says. “This research will not deliver immediate benefits. It’s a new idea, a new concept, and we need to demonstrate feasibility.”
A significant degree of progress has been made in this respect. Researchers have demonstrated that phytochromes can be activated nonlinearly with the laser source developed in the project, while the AAV viruses have been developed. “We can place the phytochromes onto the viruses, which can be delivered non-invasively to the mouse brain,” says Professor Rafailov. The next stage will be to develop the laser in a portable configuration, then it can be transferred to the project partners who are working with mice. “Our partners are trying to understand how to deliver phytochromes efficiently and are looking at how the mice react. We will be aiming to show that their brains react in the way that we want,” continues Professor Rafailov. “We are working with Huntington’s disease as a model, as our partners have deep expertise in this area.”
what’s happening in the brain, then that will be extremely useful.”
Looking to the future
The project is primarily focused on Azheimer’s and Huntington’s disease at this stage, although there is potential for further development in future and to broaden out the scope of the research. This could include addressing a wider range of neuro-degenerative conditions, as well as modifying the laser source so it can penetrate deeper into tissue. “The laser source developed in NEUROPA can only be used to treat diseases which affect the cortex, as we cannot deliver light very deep into the brain. We have certain ideas about how we can penetrate deeper into tissue, but this will require a new project,” outlines Professor Rafailov.
NEUROPA
A new era for brain therapy
Project Objectives
NEUROPA integrates cutting edge technology in lasers, phytochromes, optogenetics, viral delivery and diffusion wave spectroscopy to treat neurodegenerative diseases.
Project Funding
The NEUROPA Project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 863214.
Project Partners
• Please see website for partner details: https://www.neuropaproject.com
Contact Details
Project Coordinator, Prof. E. U. Rafailov
an infrared ultra-short, femtosecond (10 -15 of a second) pulse laser,” he outlines. The idea is to use this approach to stimulate cortical areas associated with neurodegenerative disease in a mouse model, and ultimately restore normal function. “Light in the nearinfrared wavelengths can propagate deeper into tissue, and it goes through the skull,” says Professor Rafailov. “We will use an ultra-short pulse, which gives us very high peak power.”
phytochromes will be spread around the cortex of the brain,” explains Professor Rafailov. The next step then is to precisely illuminate these phytochromes and control their activity; this is still an emerging technology, and Professor Rafailov says the priority at this stage is to demonstrate feasibility. “The main task at the moment is to show that this idea works and to demonstrate its potential, then maybe it can be taken on further in a future project,”
A further aspect of the project’s research involves developing a multimodal hemodynamic brain monitoring and imaging system to study the effects of stimulating and modulating the brain in real-time, enabling researchers to monitor what happens when the phytochromes are activated. This would represent an attractive alternative to current methods of monitoring treatment effectiveness, believes Professor Rafailov. “At the moment MRI is commonly used for brain monitoring. It’s a very good technology, but it’s extremely expensive and it’s difficult to get time to use it,” he explains. “If we can manage to develop this photonics-based new technology to monitor
Researchers are exploring the possibility of a successor project, building on the progress made in NEUROPA. “We have submitted some project proposals on how light can be used to treat different diseases,” says Professor Rafailov. “My own background is in laser physics, and we are learning all the time about potential applications in human biology.”
The non-invasive treatment of neurodegenerative disease is one possibility, with a lot of attention currently focused on developing new, more effective treatments to cope with rising demand. With European society aging, and the incidence of neurodegenerative disease set to rise further in the coming years, research into new treatment methods is widely recognised as a major priority. “We are developing a new approach to treat neurodegenerative disease,” says Professor Rafailov.
Optoelectronics and Biomedical Photonics Group Aston Institute of Photonics Technologies College of Engineering and Physical Sciences Aston University Birmingham, UK B4 7ET
T: +44 121 204 3718
E: e.rafailov@aston.ac.uk
W: https://www.neuropaproject.com
W: http://rafailov.org/
Edik Rafailov is a Professor at the Aston Institute of Photonics Technology, part of Aston University. He is aa renowned authority in the field of ultrafast lasers and biophotonics, with a publication record comprising more than 500 articles in esteemed refereed journals and conference proceedings.
A type of protein called opsins are known to detect light. These opsins can be placed in biological tissue and illuminated, then it’s possible to activate or inhibit certain cells.Prof. Edik Rafailov The project concept demonstrator.