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Scientists create messenger RNA treatment for ovarian cancer and muscle atrophy

Graphic depicting therapy in mouse model. Credit: Oregon State University/Oregon Health & Science University
Graphic depicting therapy in mouse model. Credit: Oregon State University/Oregon Health & Science University

Oregon State University and Oregon Health & Science University researchers have created a potential, first-of-its-kind messenger RNA treatment for ovarian cancer and cachexia, a muscle-wasting syndrome associated with cancer and other chronic disorders. The medication is founded on the same principles as SARS-CoV-2 vaccinations, and the researchers believe that mRNA technology, while still in its infancy in terms of therapeutic use, has enormous clinical promise for disease management. Messenger RNA transmits protein-production instructions to cells.

The results, obtained using a mouse model and published today in the journal Small, are significant because ovarian cancer is a particularly lethal form of cancer, with a five-year survival rate of fewer than 30% if it has progressed beyond the ovaries.

According to Oleh Taratula, an OSU College of Pharmacy professor stationed in Portland, most patients are unaware they have ovarian cancer until it has spread to the abdominal cavity. The only treatment available has been surgical excision of as much cancer as possible, followed by chemotherapy. Most patients respond to chemotherapy at first, although the effects are usually short-lived.

Cachexia is linked to a variety of chronic conditions, including multiple sclerosis, renal failure, cystic fibrosis, Crohn's disease, rheumatoid arthritis, and HIV, in addition to malignancies of the ovaries, stomach, lungs, and pancreas. People suffering from cachexia will lose weight even if they eat, and not only fat, but also muscular mass. The debilitating illness claims the lives of up to 30% of cancer patients.

Taratula, Daniel Marks of OHSU, and researchers at the two institutions created the novel treatment, which is based on lipid nanoparticles, or LNPs, capable of delivering mRNA that induces the development of the follistatin protein within tumour clusters. The LNPs are injected into the peritoneal cavity, which houses the abdominal organs. The follistatin created after injection acts against another protein, activin A, whose high levels have been related to aggressive ovarian cancer and cachexia.

According to Taratula, mRNA therapy can have a variety of good impacts by modifying the properties of cancer cells. It inhibits the accumulation of cancer-containing ascites abdomen fluid. It also slows disease progression and causes the creation of tiny, solid tumors that do not cling to organs and can thus be removed more readily. It also helps to maintain muscular mass, which helps to battle cachexia.

He argues that cachexia and malnutrition have serious consequences for cancer patients. Many of those patients are suffering from nutritional deficiency and chronic wasting, which limits their capacity to benefit from therapy.

According to Marks, chemotherapy is still the first-line treatment for metastatic illness, but it comes at a significant cost in terms of muscle mass loss, fat depletion, tiredness, and systemic inflammation. There is an obvious need for innovative medicines and medication combinations that increase chemotherapy effectiveness and tolerance, and we believe we have taken a significant step in that regard.

The mouse model demonstrated that mRNA therapy combined well with cisplatin, the current standard of care chemotherapeutic treatment for ovarian cancer. Mice who received both therapy concurrently lived longer and had less muscular atrophy than mice that received only one of the treatments.

Journal Information: Tetiana Korzun et al, Nanoparticle‐Based Follistatin Messenger RNA Therapy for Reprogramming Metastatic Ovarian Cancer and Ameliorating Cancer‐Associated Cachexia, Small (2022). DOI: 10.1002/smll.202204436
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