Gene Silencing: Transforming Patient Care and Drug Development

Genetic modification continues to push boundaries and advance the treatment of disease. Gene silencing is a promising new approach to patient care and drug development which targets the genetic communication system and has already proven effective in the treatment and management of genetic diseases.

Gene silencing explained

The human body contains between 20,000 – 25,000 genes. Each gene is a DNA sequence that gives instructions for making proteins, essentially telling our cells what to do and when to do it. The genetic code that carries the instructions is called messenger RNA (mRNA). Genetic research has enabled scientists to identify gene abnormalities that cause disease. Gene silencing is the process where mRNA is intercepted, thereby preventing disease – causing proteins from being made.

Gene silencing drugs, also called RNA therapeutics, replicate RNA interference (RNAi) – a natural process of gene silencing found in plants that protects them from viruses. Gene silencing drugs run interference, switching off genes by killing the mRNA before it signals the creation of abnormal proteins. By targeting mRNA, the specific proteins involved in certain diseases can be fine-tuned to control diseases.

The American Society of Gene & Cell Therapy explains that there are risks associated with gene therapy. Traditional approaches in gene therapy make permanent changes to the genetic instructions contained in the patient’s DNA. Many experts agree that gene silencing is a less risky option because only the instructions are targeted, leaving the original DNA intact. However, gene silencing isn’t a permanent change to DNA. In order for the therapy to work, the patient must continue to take gene silencing drugs, but these cutting-edge therapies now provide hope to patients with previously untreatable diseases.

According to Harry Stylli, Ph.D., founder and executive chairman of OncoCell MDx, genomics is being utilized more frequently in mainstream medicine as specialists are able to target specific genes and proteins that cause diseases. Gene silencing is a new frontier of genomics that has wide-reaching implications on the future of drug therapy and disease management.

FDA approved treatment

In August 2018, Patisiran became the first gene silencing drug approved by the FDA. Patisiran was developed to treat polyneuropathy in patients with hereditary transthyretin-mediated amyloidosis (hATTR). The life expectancy of patients with this degenerative disease is only 3 to 15 years as abnormal protein builds up, affecting the body’s peripheral nerves, heart, and other organs. Patisiran both reduces the damaging deposits and prevents the production of the abnormal protein. This medical breakthrough provides patients with significant improvement in their symptoms, as well as a more effective way to manage their disease.

A second gene silencing drug called Givosiran gained FDA approved in late 2019 for the treatment of Porphyria. In this rare genetic condition, the body doesn’t have the enzymes to create heme thus hampering the red blood cell’s ability to transport oxygen through the body. Patients experience a variety of symptoms including light sensitivity, severe nerve pain, paralysis, and in some cases death.

Givosiran lowers the production of the enzymes involved in heme production and prevents toxic proteins from building up. Patients taking this ground-breaking drug no longer rely on pain killers for disease management and many are living pain-free.

Neurodegenerative disease research

Gene silencing is also being studied for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). This incurable disease affects the motor neurons controlling voluntary muscle movement. As ALS progresses, patients experience permanent impairment of motor functions, ultimately leading to paralysis and death.

In late December 2019, researchers from the University of California, San Diego School of Medicine published the findings of their study using gene silencing in the treatment of ALS. The research team successfully suppressed ALS in mice who were treated prior to the onset of the disease. Furthermore, the researchers were able to prevent the progression of ALS and block the degeneration of motor neurons in mice in which symptoms had already appeared.

Senior author of the study, Martin Marsala, MD stated, “At present, this therapeutic approach provides the most potent therapy ever demonstrated in mouse models of mutated SOD1 gene-linked ALS.” Gene silencing is by far one of the most promising discoveries in ALS research to date and provides hope to patients who generally face a life expectancy of 2 to 5 years upon diagnosis.

Cancer research

Some cancers aren’t receptive to currently available precision-targeted genetic treatments. With cancers like these, chemotherapy is often the foremost treatment protocol. While effective in destroying cancer cells, chemotherapy treatment often causes damaging side effects in patients. A study at Scripps Research is using gene silencing to develop a compound that triggers cancer cells to destroy themselves, while not harming healthy cells. This development shows incredible promise for treating triple-negative breast cancer, melanoma, and lung cancer.

Gene silencing is an exciting development in the transformation of patient care. Doctors and scientists remain optimistic that these innovations in gene therapy will ultimately cure human disease. Cutting-edge therapies such as these provide more effective disease management and the hope of a disease-free future for patients with incurable conditions.