A geneticist wages war against ‘bad’ cholesterol

Helen Hobbs, who won the 2016 Breakthrough Prize in Life Sciences, explains how PCSK9 inhibitors work when statins don’t

February 13, 2019 11:21 pm | Updated 11:21 pm IST - Bengaluru

Helen Hobbs, a geneticist at Dallas’ UT Southwestern Medical Center, speaking at the TNQ Distinguished Lectures in Life Sciences in Bengaluru on Wednesday.

Helen Hobbs, a geneticist at Dallas’ UT Southwestern Medical Center, speaking at the TNQ Distinguished Lectures in Life Sciences in Bengaluru on Wednesday.

Several modern diseases, whether diabetes, coronary artery disease or fatty liver disease, are common among those who are obese or have insulin resistance. Yet, not everyone who has these risk factors falls sick. What differentiates those who are protected from those who aren’t? The answer lies in genetics, according to Helen Hobbs, a geneticist at Dallas’ UT Southwestern Medical Center.

“Geneticists look for people who are similar, yet different,” she said during her talk at the TNQ Distinguished Lectures in Life Sciences here on Wednesday.

Dr. Hobbs, who won the 2016 Breakthrough Prize in Life Sciences, discovered a mutation in a gene called PCSK9, which protects African Americans against heart disease. Her other discoveries include a mutation in a gene called ANGPTL3, which suppresses plasma triglycerides and cholesterol, and mutations that promote fatty liver disease in Hispanics. The first of these discoveries led to the development of PCSK9 inhibitors, drugs that work when statins don't.

At the talk, held in Bengaluru’s St. John’s auditorium, Dr. Hobbs explained how PCSK9 inhibitors trump statins. Statins work by increasing the numbers of low-density lipoprotein (LDL) receptors, which suck up LDL or “bad” cholesterol from blood. Simultaneously though, statins also increase the level of a protein called PCSK9. This protein interferes with LDL receptors, thus attenuating their effect. This is why, patients who have just begun taking statins see a large lowering of lipids first, with effects waning later.

On the other hand, Evolocumab and Alirocumab, the two PCSK9 inhibitors developed based on Dr. Hobbs’ research, directly kill the PCSK9 protein. By allowing LDL receptors to do their job, these drugs push LDL very low, thus helping sufferers of familial hypercholesteremia who don’t respond to statins.

Through her work on the Dallas Heart Study, a multiethnic cohort of African, Hispanic and European descent, Dr. Hobbs demonstrated the role of LDL in heart disease. But her team also found that those with very low LDL due to the PCSK9 mutations did not suffer side effects.

The geneticist spoke about one such study subject, a 32-year-old aerobics instructor in the Dallas cohort, who had two copies of the protective mutation. Her LDL was as low as 14 mg/dl; for comparison, 70 mg/dl is considered healthy in most people. When Dr. Hobbs and her team tested her for loss of adrenal function and other expected side effects, they found nothing. “She was healthy then; she is healthy now,” Dr. Hobbs said. The finding was a heartening one, because it meant that drugs which mimicked the effects of the PCSK9 mutations were likely to be safe.

0 / 0
Sign in to unlock member-only benefits!
  • Access 10 free stories every month
  • Save stories to read later
  • Access to comment on every story
  • Sign-up/manage your newsletter subscriptions with a single click
  • Get notified by email for early access to discounts & offers on our products
Sign in

Comments

Comments have to be in English, and in full sentences. They cannot be abusive or personal. Please abide by our community guidelines for posting your comments.

We have migrated to a new commenting platform. If you are already a registered user of The Hindu and logged in, you may continue to engage with our articles. If you do not have an account please register and login to post comments. Users can access their older comments by logging into their accounts on Vuukle.