Indications

Cancer

The American Cancer Society (ACS) provides some sobering facts about cancer in the United States. It is the number one health threat in many developed countries. Approximately one in three people will be diagnosed with the disease and one out of every four deaths is attributed to cancer. Since 1990, over 16 million people have been newly diagnosed with the disease. The National Cancer Institute (NCI) estimates that approximately 8.9 million Americans with a history of cancer were alive in 1997.

This fact may seem encouraging until a closer look at the incidence figures is undertaken. In 1990, the ACS reported that 1.13 million people in the U.S. were diagnosed with the disease. The estimated number of deaths from the disease was 520,000. Ten years on, the incidence of the disease was estimated at 1.2 million. This year, an estimated 550,000 people will die from cancer or, since 1990, 5,500,000 have died from the ailment. It appears little has changed. Much of the criticism for the apparent lack of improvement stems more from the failure to implement an effective cancer-screening program. The detection systems have been developed but people are not availing of them.

While the National Cancer Institute (U.S.) determined that Crotoxin had a unique cell-killing mechanism it was also determined that certain cancers were particularly sensitive to its action such as CNS, melanoma and lungs cancer cell lines. The highest incidence of cancer in the U.S. by disease type are approximately; Breast (180,000), Lung (168,000), Prostate (130,000) and Colon (110,000). Death from cancer occurs most frequently as follows; Lung (145,000), Colon (50,000), Breast (45,000), Prostate (35,000) and Lymphomas/Myelomas (30,000). Relative to incidence, the most lethal cancers are; Esophageal (90%), Lung (87%), CNS (70%) and Leukemias (65%).

Ireland has one of the highest cancer incidence and mortality rates in the Western world. Approximately 11,000 die from the disease each year with 28,000 new cancer cases diagnosed. Celtic Biotech has selected lung cancer for its upcoming Phase II trial. In statistics gathered in a study over the period 1994-96 in Ireland it was shown that the average new diagnoses per annum of lung and related cancers was 2332 with deaths recorded per annum of 2301. It is the most common cause of cancer deaths in males and second in females.

Pain

A consistent report of pain relief in patients being treated with CT or VRCTC-310 lead to a study to investigate analgesia induced by crotoxin. Chronic or intractable pain, which occurs in conditions such as degenerative bone diseases and cancer, is a debilitating condition which is treated with a variety of analgesic agents, and often opioid compounds, such as morphine. Morphine is a strong pain killer with rapid onset. However, it wears off quickly, patients become resistant to its effects and there is a serious potential for addiction. The data suggested that crotoxin had an activity equivalent in potency to Demerol (an opioid drug about 10 times less potent than morphine) but with slower onset and more prolonged effect. However, over 400 times more Demerol was administered compared to the quantity of Crotoxin. On a molecular basis the difference is even more acute, suggesting that Crotoxin is 30,000 times as powerful as Demerol. When Crotoxin is compared to acetylsalicylic acid (Aspirin), the difference is measured at over 300,000 times more effective.

The data further suggested that the combination of the current drugs with Crotoxin could be beneficial giving the useful rapid onset style effectiveness displayed by Demerol and the prolonged effect of the Crotoxin, in addition to the enhancement of the antinociceptive effect with Acetylsalicylic acid. Further benefits would be reduced dependence on a known addictive drug with significant side effects.

Antiviral Effects of Crotoxin

Reports by Sander et al (1958) and Clarke and Baldone (1962) that Crotalus venom had antiviral activity and that similar proteins inhibited HIV (Fenard et al, 1999) prompted an investigation of this activity in CT. CT was shown to inhibit HIV replication in peripheral blood mononuclear cells (PMBCs) in the NIH/NIAID screening program.

Crotoxin was evaluated for anti-HIV efficacy following acute infection in a PBMC cell-based assay using two clinical isolates HIV-1_WEJO (SI phenotype) and HIV-1_TEKI (NSI phenotype):

Antiviral Efficacy vs HIV-1 Viruses in PBMCs

Confirmatory studies were conducted at the University of California at San Diego (UCSD) with the results supporting the data from the NIAID screen and equivalent IC₅₀.

Antiviral Efficacy vs HIV-1 Viruses in PBMCs (UCSD)

HIV and AIDs affect over 40 million people and there is now a new threat of HIV isolates developing resistance to current drug regimes. This renders our current therapies ineffective in the fight against this serious condition. Drugs with novel mechanisms are required to combat these resistant strains and Crotoxin displays an antiviral action that is unrelated to current HIV drug products. This provides new hopes for those whose HIV therapies have been rendered useless as a result of HIV mutating in the face of treatment.

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