Projects / Programmes
Preparation of prerequisite conditions for gene therapy of hereditary eye disorders
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B620 |
Biomedical sciences |
Ophtalmology |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Gene therapy, hereditary disease, eye disease, retinal dystrophy, gene testing, visual function, database
Researchers (22)
Organisations (2)
Abstract
Genetic eye disease are a group of rare disorders caused by mutations in more than 200 genes, alltogether affecting a significant number of people ()30/100.000). The first treatment aimed to insert a nonmutated copy of a gene in the retina was approved for human use in 2017 (RPE65, LuxturnaTM), and several other clinical trials are ongoing (ABCA4, MYO7A, RPGR). Currently, the inclusion in such studies is the only option of preventing blindness for most patients with genetic eye disease.
University Eye Hospital Ljubljana, Slovenia, has a long history of research in the field of genetic eye disease under the leadership of Prof. Marko Hawlina, under whose mentorship the current project leader, Ana Fakin, also finished her PhD. In the last 20 years we have systematically, in the framework of PhD studies of Martina Jarc Vidmar, Petra Popović, Eva Lenassi, Maja Šuštar, Ana Fakin and Xhevat Lumi studied patients with several rare hereditary eye diseases (Retinitis pigmentosa, Best vitelliform macular dystrophy, Usher syndrome, Leber's hereditary optic neuropathy, Stargardt dystrophy, PRPH2-associated dominant dystrophies and ESCS syndrome) and retinal detachment. We have also determined the usefulness of various methods used for the evaluation of the visual system including microperimetry, fundus autofluorescence and optical coherent tomography, as well as electrophysiology, in the use of which the Eye hospital in Ljubljana is one of the leading centres in Europe. Ana Fakin has continued her research on a postdoctoral project at UCL Institute of Ophthalmology where she studied ABCA4 genotype-phenotype correlations under the mentorship of Prof. Andrew Webster, Prof. Michel Michaelides and Prof. Anthony Moore and has received the 2015 ISCEV Eberhardt Dodt Memorial Award for her work on electrophysiological characteristics of different ACBA4 mutations.
Gene therapy in most cases aims to stop or slow down disease progression. It can therefore take several years before the efficacy can be demonstrated, and clinical studies often employ strict inclusion criteria. It is also still uncertain which biomarkers are the most useful in demonstrating the efficacy of the treatment as visual function in patients with low vision is difficult to measure.
The main objective of the proposed research project is to provide Slovenian patients with genetic eye disease the best possible access to gene therapy. For this we will establish a clinical-genetic patient database that will contain anonymised genetic and clinical data, necessary for the involvement in the clinical studies. The new, yet undiagnosed patients will undergo next generation sequencing to obtain diagnosis. All patients will undergo detailed analysis to determine the degree of the degeneration of the retina and/or optic nerve and various different methods of examination will be evaluated. We will develop novel methods for quantitative assessment of visual function in patients with very poor vision, such as fixation guided perimetry using larger and brighter targets and virtual reality glassess for controlled testing of patient's useful vision. The results will provide standardized set of examinations needed to determine the patient's eligibility for treatment, initial morphological and functional status, and further, to determine the effectiveness of therapy on follow up. We expect to recruit first patients to clinical trials during the duration of the project.
Significance for science
The purpose of the project is to establish a system which will provide the patients with hereditary eye diseases the best possible access to gene therapy.
Using next generation sequencing we expect to find novel, unpublished mutation causing rare genetic eye disease, including those specific to Slovenian population.
Assessment of different modalities that can be used to evaluate the function of the visual system will help us determine which of these are the most reliable and useful for following patients receiving gene therapy.
Significance for the country
The purpose of the project is to establish a system which will provide the patients with hereditary eye diseases the best possible access to gene therapy.
Using next generation sequencing we expect to find novel, unpublished mutation causing rare genetic eye disease, including those specific to Slovenian population.
Assessment of different modalities that can be used to evaluate the function of the visual system will help us determine which of these are the most reliable and useful for following patients receiving gene therapy.
Most important scientific results
Interim report
Most important socioeconomically and culturally relevant results
Interim report
