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UCLA study reports viagra drug may help improve exercise capacity in pulmonary fibrosis patients

3 months ago

UCLA researchers have found that Viagra may help patients with idiopathic pulmonary fibrosis, an incurable disease characterized by progressive scarring in the lungs, which often leads to a lung transplant.

Published in the March issue of the journal Chest, the research shows that more than half of the patients treated with Viagra, also known medically as Sildenafil, improved their walking distance by at least 20 percent during a standard test to measure lung function.

Over five million worldwide suffer from this devastating disease, so we are hopeful that this drug may prove an effective therapy for pulmonary fibrosis, said the study’s principal investigator, Dr. David A. Zisman, medical director of UCLA’s Interstitial Lung Disease Program and assistant professor of pulmonary and critical care medicine at the David Geffen School of Medicine at UCLA.

Many patients with pulmonary fibrosis also have pulmonary hypertension, which constricts arteries and lessens blood flow to the lungs, resulting in diminished lung capacity and breathing difficulties. According to Zisman, Sildenafil may help breathing by opening or dilating blood vessels to allow more blood flow to the lungs.

In this pilot study, 14 idiopathic pulmonary fibrosis patients initially took a standard six-minute walking test. All patients were then given oral Sildenafil therapy for three months, followed by a second walking test to gauge performance changes.

Researchers noted that 57 percent of the patients improved their walking distance by 20 percent or more. The average improvement in walking distance was 49 meters (161 feet).

Eleven patients completed the study. Only two patients experienced side effects and had to stop the medication — one due to diarrhea and the other due to abnormally low blood pressure.

In this small pilot study, the drug was well-tolerated, said Zisman. The next step is to confirm this finding in a large, randomized clinical trial. The study was funded by the National Institutes of Health.

'Erectile dysfunction' drugs heighten natural anti-cancer activity

Thursday, 07 December 2006

Sildenafil and other impotence drugs that boost the production of a gassy chemical messenger to dilate blood vessels and produce an erection now also show promise in unmasking cancer cells so that the immune system can recognize and attack them, say scientists at the Johns Hopkins Kimmel Cancer Center.

Tests at Hopkins on mice with implanted colon and breast tumors showed that tumor size decreased two- and threefold in sildenafil-treated animals, compared to mice that did not get the drug. In mice engineered to lack an immune system, tumors were unaffected, proof of principle, the scientists say, that the drug is abetting the immune system’s own cellular response to cancer.

In a report published in the Nov. 27 issue of the Journal of Experimental Medicine, the Hopkins team says boosted levels of the chemical messenger nitric oxide appear to dampen the effects of a specialized cell that diverts the immune system away from tumors, allowing swarms of cancer-attacking T-cells to migrate to tumor sites in the rodents.

Lab-grown cancer cells treated with sildenafil showed similar results, as did tissue samples taken from 14 head and neck cancer and multiple myeloma patients.

Sildenafil, marketed under the trade name Viagra, is one of a class of drugs used to treat erectile dysfunction in millions of men, and in recent years, its ability to stimulate the production of NO has been investigated by experts in diseases linked to the activity of blood vessels and blood components.

The new Hopkins study homes in on a tactic used by cancers to avoid detection by the immune system by turning elements of that system to its own advantage, says Ivan Borrello, M.D., assistant professor at the Johns Hopkins Kimmel Cancer Center.

Borrello and his colleagues found that tumors exploit nitric oxide-producing immune cells to create a sort of fog that keeps them hidden from white blood cells (T-cells) that mount attacks on tumors.

These NO-producing cells, a.k.a. myeloid-derived suppressor cells (MDSCs), normally use nitric oxide to help bring the immune system back down to surveillance levels after an attack mode response to foreign material.

The impotence drugs seem to reverse this process, stopping the production of nitric oxide by MDSCs thereby allowing other immune cells to see the cancer and attack it, says Paolo Serafini, Ph.D., a research fellow in Borrello’s laboratory and lead author on the paper.

Nitric oxide is infamous among city dwellers as a component of air-polluting smog, but is gaining importance in medical research for its cell-signaling duties and its ability to divert soldiering T-cells that patrol and protect.

The Hopkins team also analyzed gene expression patterns of the myeloid-derived suppressor cells and found that sildenafil blocked two genes regulating enzymes -- arginase and nitric oxide synthase -- which are key to triggering immune suppression via MDSCs. Borrello’s team found that the arginase enzyme, which metabolizes a dietary supplement called L-arginine, also contributes to dampening the immune system through MDSCs much like nitric oxide, and its production can be reversed by sildenafil.

Impotence drugs won’t cure cancer, Borello cautioned, but could be used in addition to standard chemotherapy or immunotherapy treatments.

The investigators are planning human studies to begin in the next year.