The National Institute for Health and Care Excellence (NICE) has just recommended a gene silencing treatment for acute hepatic porphyria (AHP), a rare disease.

AHP

AHP is a term for four different conditions, all genetic. AHP is the result of genetic variants which lead to a build-up of porphyrins within the liver. Each condition in this family causes frequent attacks of vomiting and severe abdominal pain. Additionally, seizures, anxiety, depression, as well as other neurological conditions, are common.

Symptoms vary over time, but many patients face extended periods of pain which can lead to hospitalization. As a result, social life is extremely difficult to maintain as is a regular work schedule.

There are some treatments for AHP, but they all focus on mitigating symptoms, not on correcting the root cause. No treatment is effective at preventing pain attacks, but they can help patients feel better in the moment. That said, these treatments also have intense side effects.

The hope is that this new gene silencing approach will help patients to live a life unaffected by AHP’s symptoms.

Gene-Silencing

Some forms of gene therapy alter DNA. The gene silencing technique does not. This strategy uses RNAi. It controls the ALAS1 gene’s activity level by intercepting the mRNA from the gene. Cells are prevented from using RNA to create the enzyme.

One con to this form of treatment is that it must be ongoing to ensure the gene stays silent.

Givosiran is one of these gene silencing developments. It is a monthly injection which surpasses ALAS1. Givosiran was approved in 2020 by the EMA. It now has a recommendation from NICE for severe AHP patients. Severe AHP is defined by attacks occurring 4 times a year or more.

There is an ongoing clinical trial of Givosiran. It has so far demonstrated it is able to prevent 74% of symptom attacks. Sue Burrell, a patient in the trial, explains how life-changing the treatment has been for her. She now has a social life, has time to think through the future, and time to enjoy her life day to day.

Researchers are hopeful that this new technique could transform AHP patients’ lives. Additionally, scientists are working on developing treatments for other rare diseases using this technology. For instance, in the UK, they are working on a gene silencing technique for amyloidosis. Since this technology attacks the root cause of diseases, it has a very promising success rate.

You can read more about this new technology here.