Better Medicine

Chemistry and liquid crystal technology create a formula for hope and healing

Like a dark, sometimes deadly spider, cancer has spread its web throughout the world. Whether it’s through a family member, friend, co-worker or even ourselves, very few of us remain untouched by its venomous grasp. In fact, the American Cancer Society estimates that nearly 1.5 million new cases of cancer will occur this year alone. This crisis has led the National Cancer Institute to establish a goal of eliminating suffering and death due to cancer by the year 2015.

While that goal may seem like a stretch, the collaborative efforts of three men and the extraordinary potential of liquid crystal technology have brought it closer to our reach than ever before.

Dr. Chun-Che Tsai, Kent State professor of chemistry; Dr. Jim Jamison, manager of Urology, Obstetrics and Gynecology Core Basic Research Laboratory for Summa Health System and Kent State alumnus (B.S. ’73, M.S. ’81, Ph.D. ’86); and Tom Miller, president of IC-MedTech Inc., a California-based biotechnology company, have collaborated to develop a new paradigm in drug discovery based on the pharmacologic properties of liquid crystals called Liquid Crystal Pharmaceuticals^™, or LCPs.

This past summer, the group gathered at Kent State to file applications for two innovative patents through the university’s Office of Technology Transfer: one for a new LCP-based anti-tumor drug called Tolecine^™ and another for a formulation that combines Tolecine^™ and another LCP, Apatone^®.

Though best known for their use in laptops, televisions and cell phones, liquid crystals also include families of organic substances that are essential for all life. Called lyotropic liquid crystals, some examples include DNA, proteins and cholesterol. LCPs are a unique class of lyotropic liquid crystals that represent novel drug candidates for the treatment of a wide range of diseases.

The most recent research involving LCPs has yielded a new investigational anti-tumor drug called Tolecine^™, a compound that also has antiviral and antibacterial applications. Created by Tsai, who has been working on Tolecine^™ for seven years, it has been shown to be even more effective than the current standard of care for herpes. In preclinical laboratory tests, Tolecine^™ seems to work particularly well for skin cancers.

The team’s second patent application involves a formulation that combines Tolecine^™ and another LCP, Apatone^® to offer improved efficacy. This approach attacks cancer cells via multiple pathways. While Tolecine^™ is in the beginning stages of drug development, Apatone^® has been successfully tested in more than 30 human tumor cell lines and animals by Deb Neal, a research associate at Kent State and Summa, and Karen McGuire, a research assistant at Summa and graduate assistant in biomedical sciences at Kent State.

Apatone^®, the first LCP which combines vitamins C and K_3, was patented last year by Jamison and Dr. Henryk Taper, Catholic University of Leuven in Brussels, Belgium, Dr. Jacques Gilloteaux, American University of the Caribbean, St. Martin, and Dr. Jack Summers, Summa Health System.

From 2005 to 2007, IC-MedTech and the Beaumont Foundation supported the first FDA-approved, human clinical trial of Apatone^® conducted at Summa in Akron, Ohio, and William Beaumont Hospital in Royal Oak, Mich. This Phase I/IIa clinical trial successfully demonstrated the safety and efficacy of orally administered Apatone^® in humans for the treatment of prostate cancer. The drug demonstrated a delaying effect in the progression of end-stage cancer patients.

“Ultimately, though, Apatone^® is intended to be administered intravenously just prior to chemotherapy and then given orally in low doses to stop cancer re-growth between chemotherapy cycles,” says Jamison.

Cancer is uncontrolled cell growth during its beginning stages. Most chemotherapy drugs do not recognize the difference between healthy cells and cancerous cells. The drugs are designed to target cells that are quickly dividing, which in addition to tumor cells also can be healthy cells in a person’s stomach or intestinal lining and bone marrow.

Apatone^®, unlike other chemotherapy drugs, has low toxicity and does not target dividing cells; thus, it spares fast-growing, healthy cells. “We want to kill cancer cells specifically without killing surrounding tissues,” says Jamison.

“Apatone^® targets cancer cells and exploits some of their emergent properties in a way that allows you to turn them on themselves,” says Miller.

Normally, cells use either sugars or fats for energy. However, cancer cells rely primarily on glucose to meet their energy requirements. Specifically, these cells expand special pores on their surface to allow sugars to enter. Vitamin C in Apatone^® resembles glucose, so it preferentially accumulates in tumor cells. “But it is a Trojan horse to the tumor cell,” says Jamison, because along with vitamin C, the cancer cell also is taking in vitamin K₃, and the combination reacts to produce hydrogen peroxide within the cell.

The idea is similar to when you get a cut or scrape. After you’ve cleaned it with soap and water, you swab it with hydrogen peroxide, which kills the bacteria. In similar fashion, “when Apatone^® is broken down, it produces hydrogen peroxide, which damages the tumor cell,” says Jamison.

In addition, when the cell is stressed by Apatone^®, it needs three to four hours to recover. This provides a window of opportunity where the cancer cell cannot protect itself. “The key is to take out the defense system and then go for saturation bombing with chemotherapy before it can recover,” Jamison explains. Therefore, Apatone^® has broad-spectrum applications for treating almost any type of cancer and even leukemia, he says.

Although the FDA has not yet approved chemotherapy in conjunction with Apatone^® in humans, says Miller; that is the next step. In humans, clinical trials in which only vitamin C or only vitamin K₃ is given intravenously have been conducted, but the combination, such as that found in Apatone^®, has not been tested. Recently, though, the FDA granted Apatone^® orphan-drug status for the treatment of metastatic, or locally advanced, inoperable bladder cancer.

Innovative, low-toxicity drugs such as Tolecine^™ and Apatone^® provide new hope in the battle against cancer and other diseases in the next few years. “Research on LCPs provides an important, solid scientific foundation for generations of new drugs,” says Miller. Adds Tsai: “LCPs are an untapped frontier from which many new, exciting treatments are now emerging.”

“At the end of the day, treating diseases such as cancer more effectively is what it’s all about,” adds Miller.

 
For more information about this particular area of research, read "New Drug Paradigm: Liquid Crystal Pharmaceuticals" from Science Daily.