Currently, pharmacological treatment of degenerative diseases of the retina focuses on two main action lines:
1. In the use of preventive strategies attempting to counteract the underlying mechanisms of the disease, such as gene therapy.
2. In attempting to prevent cell death by administering anti-inflammatory and antiapoptotic compounds (e.g. a cocktail of antioxidants), as well as neurotrophic factors delaying cell death of the retina, slowing thus the progression of the disease.
Degenerative processes of the retina have a great impact on the quality of life of patients. In this sense, it is particularly interesting to find suitable pharmacological treatments.
A Spanish research group has found a chemical compound, 3-(2-isothiocyanatethyl)-5-methoxy-1H-indol (Figure 1), with a potent antioxidant and cytoprotective effect which can be used as a therapeutic strategy to avoid, prevent or mitigate retinal degeneration in diseases such as: retinitis pigmentosa, glaucoma, age-related macular degeneration and diabetic retinopathy.
In the preventive or therapeutic treatment of the degenerative diseases of the retina described above, both the discovered compound and its pharmaceutically acceptable salts can be used. These salts can be prepared from: organic acids, inorganic acids, metallic salts, ammonium salts, salts formed from organic bases, and salts with amino acids.
This compound can be easily prepared through different methods described in the scientific literature. Soluble complexes can be prepared with different excipients. The pharmaceutical composition can be administered in daily doses orally, rectally, subcutaneously, intramuscularly, intravascularly, injectablely or intravenously. It may be administered locally as a solution (e.g., eye drops, intraocular injection, or intravitreal injection), or as an implant.
Different animal models of retinal degeneration have been studied, among them:
1. Cytoprotection against sodium nitroprusside induced toxicity in the cell line derived from 661W photoreceptors: The use of the compound significantly increased neuronal survival. In fact, the viability of the 661W cell line increased up 20% respect to the control. (see Figure 2)
2. Visual responses rescue in the animal model of retinosis pigmentaria rd10: The murine strain rd10 is the most suitable model for testing therapies related to retinitis pigmentosa. Different doses of the compound administered intraperitoneally have been studied, from the beginning to an advanced stage of the degenerative process, and it has already proved that the compound exerts a protective effect, and therefore, it is an effective agent to treat retinitis pigmentosa.
3. Measurement of the amplitude of the electroretinogram (ERG): There is a certain dose of the compound (10 mg/Kg) that achieves a statistically significant improvement in the functional response of the retina respect to control (see Figure 3).
4. Measurement of visual acuity and contrast sensitivity in the murine model rd10:
Visual acuity gives a measure of the functional activity of the retina. This test showed that in rd10 mice treated with the compound (a dose of 10 mg/Kg), visual acuity increased 35.6% respect to control (see Figure 4).
Contrast sensitivity: in animals treated with the compound (a dose of 10 mg/Kg), contrast sensitivity increased between 11% and 15% with respect to the control, depending on the spatial frequency of the stimulus (see Figure 5).
Pharmaceutical companies interested in acquiring this compound for commercial exploitation through patent licensing agreement or technical collaboration agreements for development of new applications are sought.