Gene therapy will protect against heart attack
Researchers at Harvard University and the University of Pennsylvania, working under the guidance of Dr. Kiran Musunuru, have developed an approach based on the modification of the Pcsk9 gene (proprotein convertase subtilisin/kexin type 9), which makes it possible to irreversibly reduce cholesterol levels in the blood of mice with a single injection. They believe that its use in clinical practice will reduce the risk of myocardial infarction by 40-90%.
In 2003, French researchers who studied family cases of high cholesterol in the blood and myocardial infarction at a very early age, found that the PCSK9 protein is a regulator of cholesterol levels. Certain rare mutations in the gene encoding it have been associated with the above symptoms.
As part of another work, Texas researchers found that about 3% of people are carriers of mutations of this gene that have the opposite effect. The level of low-density lipoproteins ("bad cholesterol") in the blood of carriers of these mutations is 15-28% lower than the average values. In addition, these mutations reduce the risk of myocardial infarction by 47-88%.
The Pcsk9 gene is predominantly expressed by liver cells. Its protein product turns into an active form in the bloodstream, where it prevents the excretion of cholesterol from the blood. Several pharmaceutical companies are working on creating drugs that neutralize this protein or receptors sensitive to it, but such drugs have a limited duration and require regular administration.
The authors suggested that this problem can be solved with the help of a new method of genetic engineering CRISPR/Cas9, which allows to make changes to DNA with high accuracy. In experiments on mice, they managed to achieve selective modification of the Pcsk9 gene in more than 50% of liver cells. Within 3-4 days after the procedure, a decrease in the concentration of PCSK9 protein was recorded in the blood of mice. This led to an increase in the expression of receptors for low-density lipoproteins on liver cells and a decrease in cholesterol levels in the blood by 35-40%.
The researchers believe that the implementation of their developed approach in clinical practice can reduce the incidence of myocardial infarction by 90%, which is one of the leading causes of mortality and often takes the lives of quite young people.
Article by Qiurong Ding et al. Permanent Alteration of PCSK9 With In Vivo CRISPR-Cas9 Genome Editing is published in the journal Circulation Research.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from Harvard University: A shot against heart attacks?
16.06.2014