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Thursday, Aug 21, 2014

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Rathindra Bose

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New York company to develop Ohio University cancer drug discovery

Investors finance further testing of promising treatment for ovarian cancer


New York-based company Phosplatin Therapeutics has licensed a new class of anti-cancer compounds developed at Ohio University that could lead to a new chemotherapy treatment for ovarian cancer and other solid tumors.

Professor Rathindra Bose, vice president for research and dean of the Graduate College, designed and conducted the studies on the new compounds, which have successfully and safely inhibited ovarian cancer tumor progression in mice.

The compounds, called phosphaplatins, exhibit evidence of three crucial anti-cancer properties governed by genetic signals: inducing cell death in cancer cells, reducing the tumor’s demand for blood and nutrients to support its growth and preventing the spread of tumor cells. Platinum has historically been one of the most potent classes of chemotherapy drugs, but is also known to have severe toxic effects on the body which limit its use.

Bose's compounds −− a combination of phosphate and platinum −− activate specific genes, promote expression of trans-membrane proteins of cancer cells and transmit a set of signals to the interior of the cells, thereby killing them and preventing spread of the disease without damaging DNA in the cell nuclei. The compounds were also designed to overcome some patients' resistance to platinum chemotherapies and to remain more stable in the body so they are not bound to proteins, a common cause of toxicity.

Phosphaplatins have demonstrated potential to be more effective and more targeted drugs, which create fewer side effects in patients. Studies have shown that the phosphaplatins can kill ovarian cancer cells, including cells resistant to conventional drugs, at a fraction of the dosage, but at equal or greater potency.

"Scientifically speaking, this is a paradigm shift for designing platinum cancer therapeutics by targeting multiple pathways to control growth, inhibit spreading and specifically kill cancer cells without binding DNA," Bose said. "Our compound is unique in displaying all three properties in killing cancer cells and controlling their proliferation."

Robert Fallon, chief executive officer of Phosplatin Therapeutics, said he found early test results compelling enough to gather founding investors and establish the company last year.

"Dr. Bose has figured out a way to design a compound with the potency of successful platinum therapies without the commonly known damaging effects," said Fallon, who also serves as a trustee on the Ohio University Foundation Board. "The results of early testing are very, very encouraging, and his understanding of the drugs’ novel mechanism of action is profound. I saw a need to bring this into commercialization. When the research is complete, the hope is we will have a new chemotherapy drug which can positively impact patients around the world."

Ohio University has a strong track record of licensing research technology, particularly in the area of health and wellness. Royalty income – which totaled $8.2 million in 2010 – is consistently the highest of any public education institution in Ohio, the majority stemming from a license to Pfizer for another drug originally discovered at Ohio University.

"We value our partnerships with Robert Fallon and other visionaries who are committed to furthering science and its benefit to humanity," said Ohio University President Roderick J. McDavis. "These relationships have brought Ohio University researchers the opportunity to take groundbreaking research into the marketplace, where the discoveries elevate the human condition and support future research initiatives."

In a collaborative effort, Phosplatin Therapeutics has started quarterly payments to Ohio University that will total $600,000 for Bose’s laboratory to continue his work with the compounds. The research will now focus on how phosphaplatins work, how the drug distributes through the body, potential toxicity and the effects at various doses, Bose said.

The company, for which Bose will serve as a scientific advisor, will then seek to obtain an Investigational New Drug Application through the Food and Drug Administration (FDA) for human clinical drug trials.

The first drug developed for the treatment of ovarian and testicular cancers, cisplatin, was approved for use in 1982. Though it's 95 percent effective, it works best during the early stages of the disease, and some patients develop a resistance to it. Two drugs introduced later, carboplatin and oxaliplatin (which is used for colorectal cancer), overcame some of those problems, but still they can harm numerous organs and bodily systems of patients, said Bose.

Unlike cisplatin, which can decompose quickly and create additional toxic side effects through the decomposition products, the new compounds show no signs of degradation after seven days, he added.

Bose is a professor with joint appointments in the Department of Biomedical Sciences in the College of Osteopathic Medicine and the Department of Chemistry and Biochemistry in the College of Arts and Sciences. He also is a principal investigator at the Edison Biotechnology Institute, where he conducts his research.

Bose has been studying alternative compounds, molecular targets, and genetic processes for these cancers for over 20 years, including at his previous institution, Northern Illinois University, before his appointments with Ohio University in 2008.

"Dr. Bose’s work, which is the product of years of experimentation and dedication, illustrates the type of contributions that faculty at public universities can make," said Executive Vice President and Provost Pam Benoit. "He has expanded the realm of scientific knowledge in important ways while helping to sow the seeds for future discoveries through his work with graduate students and post-doctoral researchers."

Fallon said he understands the attempt to create an effective new drug is risky, but worth the investment of time and money.
"Regardless of the outcome, at the end of the day we can say we have advanced the cause of science," he said.