Importance of Safety in Drug Development

Evaluating RNA Drugs for Rare Diseases

Safety remains a critical consideration in the development of new pharmaceuticals. Researchers are currently assessing the safety and efficacy of RNA drugs designed to deliver instructions to cells, enabling them to produce proteins that are deficient in individuals with rare diseases.

Understanding Messenger RNA (mRNA)

Messenger ribonucleic acid (mRNA) plays a vital role in protein production within the genetic framework. It serves as a carrier of genetic information from DNA to ribosomes, where proteins are synthesized. Proteins are essential for the body’s various functions. mRNA drugs contain specific instructions that prompt the body to produce particular proteins, which can be instrumental in disease prevention and treatment.

Recent Advances in RNA Drug Research

Moderna Therapeutics and RNA Technology

A recent article in Science Magazine highlights advancements in RNA drug development. Moderna Therapeutics, a U.S.-based biotechnology firm founded in 2011, specializes in utilizing mRNA technology for drug development. The company has established collaborations with top pharmaceutical firms to enhance the creation of RNA drugs and vaccines across multiple therapeutic areas.

Challenges in RNA Drug Administration

The application of RNA drugs in medicine involves introducing foreign molecules into the body, which carries the risk of adverse reactions. The immune system may perceive these drugs as foreign invaders and respond accordingly. Additionally, RNA drugs can present toxicity issues, even at doses lower than those required for therapeutic effects.

Research on Methylmalonic Acidemia (MMA)

Investigating RNA Therapy for MMA

Researchers at Moderna Therapeutics are exploring the potential of RNA therapy to treat methylmalonic academia (MMA). They are testing a novel nanoparticle designed to deliver mRNA that encodes for the enzyme methylmalonyl-CoA mutase (MUT), which is either missing or defective in MMA patients. This enzyme is crucial for breaking down fats and proteins in the diet. Without it, patients can experience dangerous accumulations of methylmalonic acid in their bloodstream, leading to severe health complications such as weakness, kidney and liver damage, seizures, and strokes.

Study Findings on Safety and Efficacy

A study published in Cell Reports by Moderna Therapeutics indicated no significant safety concerns in MUT-deficient mice that received weekly intravenous injections of MUT-encoding RNA over a five-week period. Results showed up to an 85% reduction in blood levels of toxic acid, along with improvements in overall health. The article notes that the mice were monitored for several additional weeks, revealing no signs of toxicity.

Long-Term Considerations for RNA Drug Use

The Need for Ongoing Research

While these findings represent a promising development in medical treatment, it is crucial to consider that genetic diseases often require long-term medication management. As some patients may need RNA drugs throughout their lives, it is essential to gain a clearer understanding of the long-term safety implications. Continued research is necessary to ensure the safe and effective use of RNA drugs.

Author Information

Written by Anuolu Bank-Oni, Pharm.D, CDE, BCGP

References

(1) Servick, K. Can a multibillion-dollar biotech prove its RNA drugs are safe for a rare disease? Science Magazine. doi:10.1126/science.aar8088
(2) Moderna Therapeutics. www.modernatx.com. Accessed January 3, 2018