PHOTOCHROMIC MOLECULES FOR THE CARE OF DYSTROPHIES
Data di pubblicazione02-01-2019
Data di priorità06-04-2018
TitolareIstituto Italiano di Tecnologia (IIT) e Politecnico di Milano
DipartimentoDepartment of Chemistry Materials and Chemical Engineering
AutoriLanzani Guglielmo, Bertarelli Chiara, Colella Letizia, Benfenati Fabio, Di Francesco Mattia, Colombo Elisabetta, Lodola Francesco, Paternò Giuseppe, Maya-Vetencourt Jose Fernando
Retinal dystrophies, such as retinitis pigmentosa and senile macular degeneration, are caused by genetic mutations that compromise the survival of the cones and rods and there is no pharmacological treatment to prevent photoreceptor degeneration, by now.
The invention relates to a family of photochromic amphiphilic molecules that spontaneously place themselves in the cell membrane and generate a significant variation in the membrane potential following a light stimulus. These properties are particularly advantageous in the modulation of the activity of neurons, as demonstrated by the generation of firing signals following photoexcitation in neuronal networks containing synaptic blockers. Photomediable azobenzene molecules for cellular photostimulation are already known, however they are specifically bound to K + channels, blocking them in dark conditions and returning to a physiological configuration under illumination with the reopening of the channels themselves. This means that the conformational state of the photochromic molecule interferes with the cell physiology.
The molecules described here, on the other hand, do not have a specific affinity with the cellular exchange channels and are located in the phospholipid layer. These characteristics give the compounds of the invention the ability to photo-regulate membrane turnover and secretory activity, allowing to separate neuronal photostimulation from physiological activity. These molecules are used in the optical stimulation of animal cells. In particular, the molecules of the invention have proved ability to restoring the neuronal activity in the animal model and are, therefore, particularly promising in the treatment, by means of intraocular injection, of degenerative diseases of the retina, such as retinitis pigmentosa and senile macular degeneration.