Desperate need for new retinal disease treatments
UEF Bulletin 2017
Therapeutic injections revolutionised the treatment of age-related macular degeneration, and even better treatments await just around the corner.
Age-related macular degeneration, AMD, is the most common cause of visual impairment in the Western world. The disease is known in two forms: wet and dry AMD. Some 80 per cent of patients suffer from the dry form of AMD, for which no treatment currently exists. However, the more rapidly progressing wet form of AMD can nowadays be slowed down by regularly administered vitreous injections.
“Injection therapy revolutionised the treatment of AMD, but it is only a temporary solution. These injections need to be administered every couple of weeks for years or even for the rest of a patient’s life, and this is very onerous for both patients and care providers. In this respect, better treatments are under way,” says Kai Kaarniranta, Professor of Ophthalmology at the University of Eastern Finland and Chief Physician of Kuopio University Hospital’s Ophthalmology Clinic.
New treatment avenues are on the horizon, thanks to a ground-breaking discovery by Kaarniranta’s research group. His team noticed that AMD is associated with impaired lysosomal autophagy, which is an important cleaning mechanism of the fundus of the eye. Cells lose their ability to remove aged, deformed or otherwise faulty proteins, leading to protein accumulation and, eventually, visual impairment.
“We are interested in finding drug therapies capable of maintaining autophagy. We assume that this could prevent the development of both dry and wet AMD. Of course, this is just one mechanism in a very complex disease, but we have already observed that maintaining autophagy also alleviates AMD-related inflammation.”
An important partner in the quest to find new drug therapies is Arto Urtti, Professor of Biopharmacy at the University of Eastern Finland and the University of Helsinki, whose research group is looking for new drugs and retinal administration methods by using nano and polymer technology, among other things.
Retinal diseases are difficult to treat because the eye’s protective structures prevent drugs administered as eye drops from reaching the retina. Moreover, not all drugs can be administered by injections.
“Most drugs get removed from the eye too quickly for them to have a proper therapeutic effect,” Urtti says.
To solve this issue, his research group has been developing a web-like polymer that releases the drug slowly in the eye, providing a therapeutic effect that lasts several months.
In addition, injectable eye implants are also available on the market, releasing the drug in the eye over a longer period of time.
“These injectable implants haven’t really taken off, but implants formed within the eye could prove to be a better-tolerated alternative,” Urtti says.
Urtti’s group has developed a method in which polymer and lipid particles are injected into the eye to form a gel-like implant. Currently, the method is being further developed by a pharmaceutical company in Japan.
Injections would not necessarily be needed at all if an alternative method for delivering the drug to the retina was discovered.
“We are currently studying structures that bind to the retinal pigment epithelium, allowing the drug to reach its target. These kinds of drugs could be administered as eye drops or oral tablets."
Ongoing research may result in new treatments not only for age-related macular degeneration, but also for other retinal diseases such as diabetic retinopathy and retinal damages caused by glaucoma.
Drug development is supported by a virtual eye, which can be used to model the administration and passage of drugs in the eye, as well as drug concentrations achieved by using different dosages. The virtual eye is being created on the basis of experimental research; however, it will reduce the need for animal testing in the future.
“The virtual eye we are working on now can be used to model the passage of drugs in the eye both when administered as a vitreous injection and when taken orally. In due course, the idea is to supplement the model by other administration channels and also to include the cellular effects of different drugs.”
Ground-breaking research in ocular diseases and targeted drug delivery
Research into targeted drug delivery in the context of ocular diseases is one of the emerging research areas of the University of Eastern Finland. Unique even by international standards, this research has also caught the eye of funders and pharmaceutical companies. Led by Urtti and Kaarniranta, the research area is a combination of medicine, pharmacy, chemistry, materials research and modelling, and it seeks to respond to a global challenge: the number of people suffering from retinal diseases is growing in tandem with the ageing population, but no efficient treatments exist. The number of patients is estimated to reach 300 million by 2030, and several pharmaceutical companies around the world have selected ocular diseases as their strategic focus area.
Recent discoveries in research, next-generation disease models, technological advances, collaboration with pharmaceutical companies and significant levels of research funding enable scientific breakthroughs in the treatment of retinal diseases. A project led by Kaarniranta and funded by the Academy of Finland uses stem cells isolated from AMD patients to create a model of the retinal pigment epithelium, allowing for an increasingly detailed analysis of the pathogenesis and treatment of the disease. Furthermore, the Ophthalmology Clinic at Kuopio University Hospital is constantly carrying out clinical trials on new drugs in collaboration with pharmaceutical companies. Ocuther, an EU project led by Urtti, on the other hand, trains next-generation ocular drug researchers. In addition to universities, the partners include companies capable of turning research discoveries into treatments to benefit patients. Urtti is also the leader of the first Finnish project ever to secure funding from the US Food and Drug Administration, FDA. The methods developed in the project speed up the product development of drugs administered on the surface of the eye in particular, as well as authorities’ review practices relating to new drugs. For patients, this means that more affordable generic drugs will also find their way to the markets faster.