Positive results of in vivo studies with human brain tumors.
In Vivo Data Using Geron Compound Supports Telomerase Inhibition as a Treatment for Cancer
MENLO PARK, Calif., Nov 19, 2001 (BW HealthWire) -- Geron Corporation (Nasdaq: GERN chart, msgs) announced today positive results of in vivo studies with human brain tumors in a mouse model when treated with Geron's proprietary anti-cancer compound, GRN163. The studies were directed jointly by Dennis Deen, Ph.D., professor of neurological surgery at University of California, San Francisco (UCSF), and Geron scientists. The results were presented by Tomoko Ozawa, M.D., Ph.D., UCSF associate specialist of neurological surgery, at the Society of Neuro-Oncology meeting in Washington D.C. on November 17. Drs. Deen and Ozawa collaborated with Geron through a sponsored research agreement that UCSF has with Geron.
In three studies, human malignant glioblastoma (brain cancer) cells were implanted in mice and the resulting tumors were treated with GRN163. In each study, after only short-term treatment with GRN163, tumor size was reduced by 70%-80% by the end of the studies in the treated versus control mice. By the end of the third and largest study, all of the control mice had to be sacrificed because their tumors had grown too large, while only one of the nine GRN163-treated mice had a tumor that reached critical size. In all of the mice that received GRN163, tumor growth was slowed. In some cases, tumor growth was essentially blocked and in one case, the tumor completely disappeared. The brain cancer used for the studies was selected because it is a particularly aggressive
form of cancer and is resistant to current chemotherapy and radiotherapy approaches.
"These results show that GRN163 is able to effectively inhibit growth of a particularly deadly form of human cancer in a mouse model," said Richard L. Tolman, Geron's vice president of drug discovery. "These and other results encourage us to pursue GRN163 as a candidate for human clinical studies."
Developed by Geron scientists, GRN163 is a short, modified oligonucleotide compound that acts as a telomerase template antagonist. The compound binds tightly to the template domain of the RNA component in the active site of telomerase, blocking the activity of the enzyme. GRN163 was chemically modified to produce improved cellular uptake and biodistribution as well as resistance to degradation and enhanced binding affinity to telomerase. GRN163 inhibits purified telomerase at extremely low concentrations and does not inhibit other critical enzymes. This suggests that, unlike most other cancer therapies today, GRN163 should have little or no toxicity in normal (telomerase-negative) tissue.
Telomerase is an enzyme that extends telomere length and rewinds the molecular "clock," thereby extending cellular replicative capacity. Most normal cells do not express telomerase. In contrast, telomerase is expressed in all human cancer types, including breast, lung, colon, prostate, myeloma and lymphoma, as well as glioblastoma. Telomerase plays a critical role in enabling the long-term survival of cancer cells. Therefore, it is a highly specific and universal target for anti-cancer therapies.
Geron has an extensive international portfolio of intellectual property covering all aspects of telomerase, including more than 60 issued patents and over 180 pending patent applications. The portfolio includes U.S. patents for purified human telomerase, the cloned genes encoding the RNA and protein components of human telomerase, telomerase activity assays and methods of screening for telomerase inhibitors. The nucleotide sequence of GRN163 is covered by an issued U.S. patent, and Geron has pending patent applications worldwide covering all aspects of the chemical composition and various formulations of GRN163 as well as methods of using this compound for the treatment of cancer.
In August 2001, Geron's collaborating partner, Kyowa Hakko Kogyo Co., Ltd. (KH), selected GRN163 for development as an anti-cancer drug. The Geron/KH collaboration includes the development and marketing of telomerase inhibitors for the Asian market. Geron retains all rights in North America, Europe and the rest of the world outside Asia. Geron will co-develop GRN163, including the joint filing of an Investigational New Drug application and management of clinical trials in North America and Europe.
END. |
