Tuesday, August 4, 2020

A single shot medicine can cure heart disease permanently

Raised cholesterol significantly increases the risks of heart disease. Globally, a third of ischaemic heart disease is attributed to high cholesterol, specifically the LDL (low-density lipoprotein) cholesterol that is the source of artery-clogging plaque. There are various medicines available in the market produced by different drug companies to tackle the cholesterol levels in the body. Though these medicines are administered continuously and are even expensive, it doesn’t find its cure permanently. Researchers are developing a molecular method named CRISPR gene editing to treat the condition permanently. By this method, they have disabled two genes in monkeys that raise the risk of heart complications. They targeted the two genes PCSK9 and ANGPTL3 and further edited by CRISPR.

PCSK9 gene

Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is an enzyme produced by the PCSK9 gene which relies on chromosome 1 and is responsible for regulating cholesterol homeostasis. This protein binds to the receptor for low-density lipoprotein (LDL), which typically transport more cholesterol within the extracellular fluid. The LDL receptor binds and initiates the ingestion of LDL- particle from the extracellular fluid into the cells. If the PCSK9 is blocked, more LDL receptors are recycled and thus contribute to less LDL- cholesterol in the blood.

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ANGPTL3 gene

The protein coded by this gene is a member of the angiopoietin-like family of secreted factors. It is mostly expressed in the liver cells, and it acts by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), thereby increasing plasma triglyceride, LDL-cholesterol, and HDL-cholesterol levels.

The trial

Researchers at Verve Therapeutics, led by Dr. Sekar Kathiresan, have focused on finding the solution for heart disease by editing the genes. The medicine consists of two pieces of RNA that are used to carry the CRISPR molecule to the indented site on the genome. It directs the editor to a single sequence of 23 letters of human DNA among the genome’s 32.5 billion letters. The RNA is covered by lipid molecules to protect the medicine from degradation. The lipid molecules travel directly to the hepatocyte, and once the RNA finds its match, it changes a single letter of the sequence to another, thereby causing the genes to break down. This study was done in 13 cynomolgus monkeys and noticed that there were no adverse effects among the macaques. After gene editing, the monkeys’ LDL levels dropped by 59 percent within two weeks. And also, ANGPYL3 gene editing led to a 64 percent reduction in triglyceride levels. There have also been reports that the people who inherit a mutation in these genes do not develop any cardiac diseases.

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There are various studies involving mice to prevent heart problems, and it too succeded at times. But Dr. Kathiresan’s study is the first to use the pencil-and-eraser type gene editing in the primates for a common disease. He also added that it would be one-and-done treatment, and there will be no requirement for the patients to undergo the same treatment again. But it is so soon to declare that the treatment is effective and safe after a single clinical trial. Even an uncommon side effect can cause serious problems in most of the people. After analyzing everything, we will make sure to use this novel method on humans so that it would help poorer countries to get off the condition in the future.

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Source: The NewYork Times

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