Ranpirnase is a ribonuclease enzyme. It breaks down the genetic material RNA into smaller components and thereby renders the cell dysfunctional. (A ribonuclease is an enzyme that degrades RNA, by definition.) It is under investigation for treatment of mesothelioma.
According to a press release from the drug company Alfacell, ranpirnase is well tolerated in humans with “no evidence of cardiac toxicity or life-time exposure limit as with doxorubicin or other anthracyclines.” Accoring to NYU medical school researchers “ranpirnase exerts antiproliferative and cytotoxic effects in vitro and in vivo.”
How it Works
When a cancer cell divides it uses RNA to help form a new copy of itself. Ranpirnase works by breaking down RNA which is used to code for a cell’s DNA thus killing or disabling a cell. Many chemotherapy drugs work by interfering with cell division, but the great thing about ribnucleases is that they appear to selectively attack malignant cells. The ranpirnase molecule is 105 amino acids long. It is derived from amphibian eggs.
Investigators found that ranpirnase does not induce myelosuppression, mucositis, alopecia, cardiotoxicity, coagulopathy, hepatotoxicity, or adverse metabolic effects.
A doctor from Columbia University, Dr. Robert Taub, presented a Phase II trail in which one-hundred and five patients with advanced Malignant Mesothelioma (MM) were treated with ranpirnase. The drug was administered intravenously used in a dose of 480 mcg/m2 once a week. The results of the tests were favorable when compared to other treatments with a median survival rate of 5.8+ months, a one-year rate of 31%, and a two year rate of 20%. In response to those results, a Phase III test was conducted to compare the efficacy of ranpirnase versus doxorubicin in patients with unresectable malignant mesothelioma. A doctor from the University of Chicago, Vogelzang, presented the results that survival times were similar for both groups. However, it was discovered that there were more patients with poor prognastic factors in the ranpirnase group, so when they were removed, the results fell in favor of ranpirnase. Yet another study is being conducted to measure the effectiveness of ranpirnase through a trial where some will take doxorubicin as a single-agent and the rest will take doxorubicin and ranpirnase in conjunction.
A more recent study conducted at the University of Pennsylvania klooked at the anti-tumor efficacy of ranpirnase on a variety of solid lung cancer tumors grafted on to naked mice. The results were that tumor growth was inhibited both in vitro and in vito and apoptosis was encouraged. Also, they found that it was more effective to use several small doses as opposed to large, singular doses. In addition, they found that a combination of ranpirnase and cisplatin would inhibit the growth of tumors even in those previously treated unsuccessfully with cisplatin.
More on chemotherapy for mesothelioma.
Antibody-onconase conjugates: cytotoxicity and intracellular routing.
Onconase cytotoxicity relies on the distribution of its positive charge.
Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma.
