Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and ultimately fatal lung disease characterized by scarring (fibrosis) of lung tissue. Over time, this scarring stiffens the lungs, making it increasingly difficult to breathe and deliver oxygen to the body. The cause of IPF is unknown, and the disease typically affects individuals over 50.

While current treatments may slow disease progression, they do not stop or reverse fibrosis. The median survival time after diagnosis is only 3 to 5 years, and many patients still face a lack of truly effective and well-tolerated therapeutic options.

Our research group demonstrated that targeting amphiregulin (AREG) by SAMiRNA significantly reduced fibrosis in the bleomycin-induced pulmonary fibrosis mouse models.

Photo by IPFeditor, via Wikimedia Commons, licensed under CC BY-SA 3.0.

Chronic kidney disease (CKD) is a progressive condition in which the kidneys gradually lose their ability to filter waste and excess fluids from the blood. It affects approximately 10% of the global population and often leads to serious complications, including cardiovascular disease and kidney failure. Among its causes, diabetes is the most common, giving rise to a specific form of CKD known as diabetic kidney disease (DKD).

Despite advances in managing diabetes and blood pressure, current treatments for CKD and DKD primarily aim to slow disease progression rather than reverse or cure it. Many patients continue to progress to end-stage kidney disease, requiring dialysis or transplantation, both of which carry significant burdens and risks.

Preclinical studies performed at siRNAgen Therapeutics showed that SAMiRNA targeting amphiregulin (AREG) could reduce kidney fibrosis by which CKD and DKD are driven.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive and potentially life-threatening liver disease characterized by fat accumulation, chronic inflammation, and liver cell injury. Over time, MASH can lead to fibrosis, cirrhosis, liver failure, and even liver cancer.

MASH is closely linked to obesity, type 2 diabetes, and insulin resistance, and affects millions of people worldwide. However, most patients remain undiagnosed until the disease has significantly progressed.

Despite the growing prevalence and severity of MASH, there are currently very few approved therapies, and no treatment reverses the disease. The complex pathogenesis, involving metabolic, inflammatory, and fibrotic pathways, presents significant challenges to drug development. There is an urgent unmet need for effective and safe therapies that can halt or reverse liver fibrosis and improve long-term outcomes in patients with MASH.

Our research group recently demonstrated that the inhibition of amphiregulin (AREG) using the SAMiRNA platform reduced hepatic lipid accumulation and attenuated fibrosis in a murine steatohepatitis model, which is under review for publication.

Cancer is a complex and challenging group of diseases characterized by the uncontrolled growth and spread of abnormal cells. In a healthy body, cells grow and divide in an orderly fashion. However, cancer cells bypass these natural controls, forming masses of tissue called tumors that can invade and destroy healthy body tissue.

Amphiregulin (AREG) plays a crucial role in promoting cancer cell proliferation, survival, angiogenesis, invasion, metastasis, and the development of drug resistance. Elevated levels of circulating AREG have been identified in multiple cancer types.

Thereby, inhibition of AREG has been shown to sensitize tumor microenvironment to chemotherapy, immunotherapy, and radiotherapy. Targeting of AREG has shown promising results in decreasing both PD-L1-mediated immunosuppression and chemoresistance in preclinical tumor models. AREG blockade enhanced the efficacy of anti-CD47 immunotherapy along with radiotherapy, effectively inhibiting metastatic proliferation.

Figures retrieved from our review article (Int. J. Mol. Sci. 2025, 26(14), 6945)

Osteoarthritis (OA) is the most common form of joint disease, affecting over 500 million people worldwide. It primarily impacts weight-bearing joints such as the knees, hips, and spine, but can also affect the hands and other joints. Characterized by the gradual breakdown of cartilage and underlying bone, OA causes chronic pain, stiffness, swelling, and loss of joint mobility. As the disease progresses, it significantly reduces patients’ quality of life and limits their ability to perform everyday activities.

Available treatments mainly focus on managing symptoms through pain relief medications, physical therapy, or intra-articular injections. However, these options do little to halt the underlying degeneration of cartilage and joint structure. In advanced cases, patients may require joint replacement surgery, which is costly and invasive. The absence of disease-modifying therapies leaves a significant gap in patient care.

At siRNAgen Therapeutics, we are pioneering OA treatments with the goal of transforming the standard of care. Our approach targets the underlying biology of the disease, aiming to control inflammation and protect cartilage. By utilizing SAMiRNA platform, we are working to deliver long-term relief and restore mobility to millions of patients suffering from OA.