Genetic Medicine: The Key to Unlocking Cures in Chronic Diseases

Imagine a medicine so targeted it pinpoints the genetic cause of a disease—at the DNA or RNA sequence level—and treats it right at the root. Only a short time ago, that concept seemed impossible, but as we’ve increased our understanding of biology and genetics, and had significant advancements in biotechnology, scientists are on the cusp of treatments—and cures—for some of our most devastating diseases.

When we talk about progress in DNA and RNA-based therapies—referred to as genetic medicine—the conversation often leads to the impact this innovation could have on rare diseases or areas where we haven’t made significant progress with traditional, non-genetic-based therapies. While the impact in diseases like Huntington’s disease or Gaucher’s disease would be significant, advancements in genetic medicine could also move us leaps and bounds in more common, chronic disease areas.

Genetic medicines make up more than 25% of our therapeutic pipeline at Lilly. Our emerging therapies in this category have the promise to significantly change the lives of 415 million people living with diabetes, obesity and cardiovascular disease.

These are diseases that require constant, life-long management, and often people living with these conditions are unable to maintain treatment. The innovation on the horizon means these chronic diseases could be managed in an entirely new way—genetic medicines have the potential to be far more targeted and dosed infrequently.  

How Could Genetic Medicines Target Cardiovascular Disease? 

Cardiovascular disease refers to a group of disorders of the heart and blood vessels. In the field, scientists have made the most progress studying genetic medicines related to this disease area. Ruth Gimeno, group vice president of Diabetes and Metabolic Research at Lilly, is spearheading our genetic medicine application to cardiovascular disease.

“In cardiovascular disease, we know that an individual’s genetic profile contributes significantly to their overall disease risk,” Gimeno said. “Scientists have made great strides in identifying specific genes that predispose or protect people from cardiovascular disease, and we see significant promise in how we can leverage this information to more precisely target the causes of cardiovascular disease.”

There are proteins (Lpa(a), ANGPTL3 and ApoC3) derived from the liver that regulate how the body metabolizes lipids (including cholesterol). People who inherited beneficial variants of these proteins can better reduce lipid levels, helping protect them from cardiovascular disease. Individuals with detrimental variants, that increase the levels of harmful lipids, may experience early onset disease.

Our siRNA-based therapies are designed to block production of certain proteins, mimicking beneficial variants. Remarkably, the effects of a single siRNA dose can last for months or potentially even a year, making these therapies very durable.

By addressing cardiovascular risk factors that cannot be managed with conventional approaches, these siRNA-based therapies address a significant unmet medical need in cardiovascular disease, while at the same time making treatment easy and more convenient for patients.

In the future, we envision that genetic medicine can go beyond treating diseases to providing cures.Using a technology called gene editing, it is possible to insert beneficial genetic variants directly into an individual’s genome. This would permanently convert a detrimental gene to a beneficial one. With this, we may be able to create a one-and-done treatment for people at high risk of cardiovascular disease based on their genetic make-up.

Advancements in Gene Therapies for Diabetes, Obesity

While cardiovascular disease leads the way in genetic medicines, these therapies also have great potential to transform the way we treat diabetes and obesity. These are common diseases that affect millions of people. In diabetes, pancreatic beta cells—the cells that make insulin—are destroyed by an autoimmune assault or become non-functional under conditions of stress.

“The targets we'd like to modulate in beta cells often can't be addressed with traditional modalities,” explained Gimeno. “If we can figure out how to deliver genetic medicines to the beta cell, we could modulate causative genes and potentially restore beta cell function.

For both diabetes and obesity, hundreds of genetic variants that contribute to disease severity and progression have been identified. If we can understand which constellation of genes most predisposes to certain diseases and identify genetic levers that most effectively decrease disease risk, we may be able to use genetic medicines to pursue entirely new classes of treatments for these diseases, possibly allowing more precise tailoring of therapies and maybe even cures.

“In obesity, we are at the cusp of having truly effective therapies for chronic weight management, but these will need to be dosed on an ongoing basis. Genetic medicine has the potential to bring infrequently dosed medicines to the obesity space, making this a much more easily managed condition,” Gimeno added.

Our Hope for the Future 

We have several early-phase clinical trials studying genetic medicines across diabetes, cardiovascular disease, neurodegenerative diseases and immunological disorders. Our increased focus and commitment to advance RNA and DNA-based medicines is fueled by the $700 million investment in the Lilly Institute for Genetic Medicine, moving to a new headquartersin 2024.

The possibilities to come from genetic medicine are potentially limitless. That means new-found hope for millions of people—those living with currently untreatable diseasesand those living with chronic, hard-to-manage diseases.  

Ruth was recently named one of the top 20 women leading biopharma research and development in Endpoints’ Women in Biopharma 2022 awards. Learn more about her trailblazing work in diabetes, obesity and cardiovascular diseases at Lilly here. 

Learn more about genetic medicines by listening to The Elixir Factor podcast and take a look inside Lilly’s labs in Cambridge to see cutting-edge innovation in genetic medicine.