Nanoparticles cured mice of myodystrophy
Researchers at Washington University in St. Louis, working under the guidance of Professor Samuel A. Wickline, demonstrated the ability of resveratrol-loaded nanoparticles to improve the symptoms of Duchenne myodystrophy in a mouse model of the disease.
Duchenne myodystrophy is a severe hereditary disease with an X-linked type of inheritance. Usually, patients with such a diagnosis are confined to a wheelchair by the age of 12 and die of heart or lung failure before the age of 30.
The mutation causing this disease is located in the gene encoding dystrophin, a protein necessary to maintain the integrity and functioning of muscle cells. Moreover, as a recent study has shown, the cells of patients with Duchenne myodystrophy are not capable of effective autophagy – the process of splitting and reusing waste products of cellular metabolism.
Despite the fact that the role of dystrophin in the self-purification of muscle cells is not clear, experiments have shown that stimulation of autophagy improves the strength of skeletal and cardiac muscles in a mouse model of the disease.
Muscle tissue of the diaphragm of a mouse model of Duchenne myodystrophy (left).
On the right side of the image, nanoparticles (red) penetrated into the diaphragmatic muscle are visible.
The authors used nanoparticles consisting of a perfluorocarbon nucleus with a diameter of 200 nanometers, the surface of which was covered with rapamycin molecules, to stimulate autophagy in the muscle cells of mice with simulated Duchenne myopathy. This drug is used as an immunosuppressant to prevent rejection of donor organs, but recent studies have demonstrated its anti-inflammatory properties and the ability to stimulate autophagy.
When injected into the bloodstream, nanoparticles accumulated in areas of inflammation, where they gradually released rapamycin, which subsequently penetrated into muscle tissue. As a result, the grip strength of the animals' paws increased by 30%, while there was also a significant improvement in cardiac function, manifested by an increase in the volume of blood pumped by the heart.
The authors also note that the use of nanoparticles makes it possible to introduce significantly smaller dosages of the drug, since oral administration of 10 times higher doses of rapamycin did not have a positive effect on the condition of animals.
Currently, corticosteroid medications such as prednisone are used to treat Duchenne myodystrophy. This prolongs the duration of the period during which patients retain the ability to walk. However, steroid hormones cause undesirable side effects, including weight gain, bone fragility and increased blood pressure.
The researchers note that the mechanism of action of steroids in this case is unknown. It is quite possible that they also increase the activity of autophagy, which indicates the possibility of using combination therapy involving simultaneous administration of corticosteroids and rapamycin-loaded nanoparticles in lower doses.
Article by K. P. Bibee et al. Rapamycin nanoparticles target defective autophagy in muscular dystrophy to enhance both strength and cardiac function published in The FASEB Journal.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Washington University in St. Louis:
Nanoparticles treat muscular dystrophy in mice.
13.02.2014