HIV Therapy Viracept May Benefit Systemic Sclerosis Patients, Mouse Study Shows

Viracept (nelfinavir mesylate, NFV), an antiretroviral drug approved as a therapy against the human immunodeficiency virus (HIV), could be beneficial in the treatment of systemic sclerosis (SSc), a study on a mouse model of the disease shows.

The study, “The Antiretroviral nelfinavir mesylate, a potential therapy for systemic scleroderma,” was published in the journal Arthritis & Rheumatology.

Viracept, formerly known as AG1343 and marketed by ViiV Healthcare, can inhibit the transformation of important cells called fibroblasts and halt the signaling of transforming growth factor (TGF)-beta1 in human lung fibroblasts and a mouse model of SSc.

TGF-beta1 is an established player in SSc development, as it promotes the transformation of fibroblast cells into collagen-forming cells called myofibroblasts. This fosters deposits of collagen, a fibrous protein, which precedes fibrosis.

Viracep in combination with other therapies is approved as a treatment for HIV infection. Recently, the drug was found to have broader effects that may be useful in the treatment of recalcitrant fibrotic lung diseases.

Therefore, the research team aimed to “determine whether nelfinavir mesylate (NFV) … can be repurposed to treat pulmonary fibrosis in systemic scleroderma (SSc).”

The team used human fibroblasts collected from the lungs, skin, and cardiac ventricle of healthy people, as well as lung fibroblasts isolated from SSc patients.

Incubating the cells with Viracept before exposing them to TGF-beta1 inhibited myofibroblast transformation in normal lung, skin, and heart fibroblasts, as well as in lung fibroblasts from SSc patients.

The team conducted further experiments to determine Viracep’s effects on established lung fibrosis. Healthy lung fibroblasts were treated with TGF-beta1 to stimulate their differentiation into myofibroblasts. After incubation with Viracep, researchers observed that the drug induced destruction of collagen molecules by activating an intracellular degradation pathway called autophagy.

In order to evaluate Viracept’s potential therapeutic effects in PF, researchers used a bleomycin-induced animal model of SSc, an established model of the disease.

An analysis of the animals’ lungs revealed that Viracept significantly reduced the percentage of lesions and collagen deposits when compared to controls.

Overall, the results suggest that Viracept prevents myofibroblast transformation in several tissues, particularly in lung fibroblasts, and increases the rate of collagen degradation in these cells.

The study focused on a particular type of cell that is important in connective tissue, the fibroblast, but “future studies are needed to determine the effect of NFV on airway epithelia, endothelium and immune cells, considering their relevance in the pathophysiology of SSc,” the team emphasized.