The risk of heart attack may be drastically reduced through gene therapy by utilizing Crispr-Cas9 to target genes that raise levels of low-density lipoprotein (LDL), reports The Guardian. Scientists in US are planning to launch a trial of the therapy in patients with a rare genetic disorder, homozygous familial hypercholesterolaemia (HoFH).
Certain mutations can dramatically lower the natural levels of low-density lipoprotein (LDL) in individuals that could help reduce the risk of heart attack. For example, some people who may carry only one, instead of the usual two, functional copies of a gene called PCSK9 tend to have extremely low cholesterol levels.
The gene therapy aims at modifying genes in the liver that are involved in making LDL rather than targeting the heart itself. LDL, often referred to as ‘bad cholesterol’ tends to build up in arteries with age, ultimately causing a blockage leading to heart attack.“These people are healthy and remarkably resistant to heart attack,” said the lead researcher Sekar Kathiresan, a cardiologist and geneticist at Harvard Medical School.
The treatment will inject scores of tiny, fatty spheres called nanolipids into the bloodstream which will enter the liver cells. Inside the cells they release a molecular gene editing kit known as Crispr-Cas9. The Crispr-Cas9 finds and disables PCSK9 or a similar gene. The aim of this procedure is to turn off about 30% to 40% of PCSK9 to mimic the natural mutation that protects against heart attacks.
Researchers at the University of Pennsylvania have already utilised genome editing to modify PCSK9 in mice and reduce their cholesterol by 35% to 40%. Once the follow-up trials will work in monkeys the scientists will launch a trial in patients with homozygous familial hypercholesterolaemia. HoFH is a rare genetic disorder that causes very high cholesterol which can be hard to control even with statins or other medicines. These patients often have heart attacks in their 30s and 40s.
“We really think we can turn the tide against coronary disease by moving from a chronic care model to a one-time treatment.” said Kathiresan.
However, some scientists foresee difficulties in offering the injection to all patients due to the risks accompanying gene therapies. They point out that it may be hard to control how many genes are turned off and to ensure that only target genes are edited.
Once the treatment proves safe and effective in the patients, doctors are planning to seek approval to offer the injection to a wider population.