Hematological malignancies are cancers that affect blood, bone marrow, and lymph nodes, and include leukemias and lymphomas. They are also referred to as blood cancers or liquid tumors. Hematological malignancies result from improper production, function, and proliferation of blood and lymph cells. Despite treatments including chemotherapy, radiotherapy, or bone marrow transplant, the disease remains poorly controlled in many patients.

Specific microRNAs are key regulators of the production of blood and lymph cells, the normal immune function of these cells, and the control of cell proliferation. MicroRNA-based drugs that coordinately regulate the multiple biological pathways that underlie the development and maintenance of hematological malignancies will provide much-needed therapeutic benefit for these patients.

Tissues and organs in the body respond to injury through a wound-healing response involving formation of fibrous scar tissue that is characterized by deposition of extracellular matrix proteins like collagen and elastin. In the setting of chronic stress that accompanies many disease processes, however, progressive accumulation of fibrotic tissue impairs the function of vital organs like the heart, lungs, liver and kidney and is a major (and largely untreatable) contributor to morbidity and mortality. In the skin, abnormal fibrotic responses can produce excessive scarring or conversely, defects in wound healing.

Discoveries by miRagen researchers and others have identified specific microRNAs that are powerful regulators of extracellular matrix production, pro-fibrotic signaling, and the cellular changes that accompany fibrosis. New microRNA-targeting drugs that coordinately modify multiple pro-fibrotic pathways will provide urgently needed novel therapeutic approaches for the treatment of pathological fibrosis.

Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig’s disease, is a neurodegenerative disease characterized by rapidly progressive muscle weakness and wasting throughout the body. ALS patients have trouble moving, speaking, swallowing, and breathing. Most of those afflicted with the disease ultimately succumb to breathing problems, typically within 3-5 years of initial symptoms. Improvements in survival with existing drug treatments are modest and new therapeutic approaches are urgently needed.

Particular microRNAs control inflammation and immune cell activation that are implicated in ALS pathology. Therapeutic regulation of these microRNAs may reduce tissue destruction and improve survival for patients suffering from this devastating disease.

Cardiovascular disease is a broad class of disorders of the heart and blood vessels, primarily manifesting in the forms of coronary and peripheral artery disease and stroke. The underlying causes of cardiovascular disease are complex and difficult to treat, and include atherosclerosis (“hardening” of the arteries), hypertension (high blood pressure), obesity and age-related vascular changes as well as genetic and environmental factors.

The costs of cardiovascular disease measured by human lives and economic impacts are staggering. As the leading cause of death worldwide, the WHO estimates that by 2015 cardiovascular disease will claim nearly 20 million lives annually. Over a third of the adult U.S. population suffers from at least one form of cardiovascular disease, resulting in a large and growing economic burden. According to the CDC, in 2010 the total annual cost of treating cardiovascular disease in the U.S. was $444 billion, exceeding the total cost of cancer ($264 billion) and representing nearly 17% of total health care expenditures.

Despite the urgent need for new drugs, the complex, multifactorial nature of cardiovascular disease has posed significant challenges for traditional “single target-single mechanism” drug development approaches targeting receptors, ion channels or enzymes. Recent discoveries uncovering the roles of microRNAs as modulators and markers of cardiovascular disease have offered unanticipated insights into pathogenic mechanisms and have opened the way to fundamentally new therapeutic strategies for the treatment of these intractable and deadly diseases.