A groundbreaking study published in PNAS reveals that an RNA nanoparticle therapy has the potential to prevent the spread of multiple myeloma (MM), a type of bone marrow cancer, in mice. Administered alone or in combination with an FDA-approved MM drug, the therapy demonstrated reduced tumor burden and increased survival rates in the mouse model. This research, conducted by scientists at the University of Pennsylvania School of Engineering and Applied Science, presents a promising avenue for treating this incurable disease.

Understanding Multiple Myeloma: Multiple myeloma affects plasma cells, a type of white blood cell found in the bone marrow. These cells produce antibodies that aid in fighting infections. However, MM leads to the production of abnormal proteins that negatively impact various bodily functions, including kidney health and blood cell production. The aggressive nature and rapid mutation rate of MM make it challenging to treat effectively. In 2020 alone, MM was responsible for over 100,000 deaths worldwide, and patients with advanced and chemotherapy-resistant MM typically have a survival rate of just six to nine months. Innovative therapies are urgently needed to improve patient outcomes.

Switching Off Cancer Spread: The researchers developed an RNA nanoparticle therapy capable of “switching off” the pathways that MM cells utilize to spread throughout the body. The treatment specifically targets endothelial cells, a significant component of the bone marrow microenvironment. These cells produce cyclophilin A (CyPA), a protein involved in protein folding, transportation, and activation of T cells during illness. In individuals with MM, endothelial cells can overproduce CyPA, which attracts MM cells to the bone marrow and facilitates their spread, resembling a “chemical GPS.”

The Novel Therapy: To disrupt the cancer-attracting signal in endothelial cells, the researchers utilized RNA therapy to silence CyPA production. However, delivering nucleic acids to the bone marrow presented a challenge due to biological barriers. Consequently, the team redesigned the delivery vehicle to create a hybrid nanoparticle capable of delivering small interfering RNA (siRNA) to endothelial cells. The siRNA effectively halted CyPA production, preventing the spread of cancer cells in vitro. In mouse models, both when administered alone and in combination with chemotherapies, the therapy demonstrated reduced tumor size, increased survival rates, and decreased resistance to chemotherapy.

Unlocking New Avenues for Treatment: This research holds the potential to overcome a long-standing barrier in MM treatment by effectively blocking cancer spread throughout the body. Dr. Michael Mitchell, co-senior author of the study, highlighted the significance of targeting the microenvironment rather than the cancer cells themselves. The team’s innovative platform for targeted nanoparticle development offers promise not only for improving MM treatment but also for addressing other cancers that spread through blood vessels. Future endeavors for the research team include identifying additional targets for this therapy and exploring the possibility of silencing other functions in cancer microenvironments to overcome cancer initiation, spread, and drug resistance. With further studies to establish safety in larger animal models, the RNA nanoparticle therapy may advance to clinical trials in humans.

Conclusion: The development of an RNA nanoparticle therapy that can inhibit the spread of multiple myeloma represents a significant breakthrough in cancer research. By specifically targeting endothelial cells and silencing cyclophilin A production, this therapy disrupts the cancer-attracting signal in the bone marrow microenvironment. The promising results observed in mice, including reduced tumor burden and increased survival rates, pave the way for potential improvements in multiple myeloma treatment. The researchers’ platform for targeted nanoparticle development offers exciting possibilities for investigating other cancers and diseases with overexpressed cyclophilin A. As safety studies progress, the RNA nanoparticle therapy holds the potential to advance to human clinical trials, bringing hope to patients affected by this challenging disease.

By Impact Lab