Experimental drug against macular dystrophy
Researchers at the University of North Carolina, working under the guidance of Associate Professor Sai Chavala, demonstrated in experiments on mice that drugs of the MDM2 inhibitor class trigger the degradation of abnormal blood vessels, leading to vision loss in macular degeneration (macular degeneration).
Macular degeneration is the most common cause of blindness among the population of Western countries. The most common age-related form of the disease begins with the so-called "dry" macular dystrophy, characterized by blurred vision and the appearance of "blind" spots in the center of the visual field.
This is how a healthy person and a patient with macular degeneration see the same streetIn about 20% of cases, the disease progresses and turns into a "wet" form, in which abnormal blood vessels form under the retina, through the walls of which fluid begins to seep, which leads to complete loss of vision.
On the left – the normal vascular network of the mouse retina, on the right – hemorrhages under the retina
in a patient with a wet form of macular dystrophy (photos by Chavala lab).
The most effective of the currently available methods of treating macular dystrophy is an injection of a drug into the eye tissue once every 1-2 months, the active ingredient of which is antibodies against vascular endothelial growth factor (anti-VEGF).
In experiments on cell cultures and mice, the authors showed that, unlike anti-VEGF, which block the activity of vascular growth factor, MDM2 protein inhibitors act directly on the formed vessels, causing their degradation.
The main function of MDM2 in the cell is the destruction of the p53 protein, the main molecular regulator of apoptosis – programmed cell death. Apparently, activation of p53 in cells of abnormal blood vessels in the retina initiates their death.
The use of MDM2 inhibitors is also associated with a number of obvious advantages over another experimental therapeutic approach currently undergoing clinical trials – low-dose radiotherapy. The mechanism of its action consists in DNA damage, accompanied by an increase in the level of p53 in cells and the launch of apoptosis processes.
MDM2 inhibitors have a similar effect without causing DNA damage. Moreover, drugs of this class can be injected into the eye tissue in the form of an injection, whereas the proposed radiotherapy approach requires surgical intervention.
Article by Sai H. Chavala et al. Retinal angiogenesis suppression through small molecule activation of p53 is published in the Journal of Clinical Investigation.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the University of North Carolina:
UNC research points to promising treatment for macular degeneration.
16.09.2013