IN VIVO STUDIES
PRTX-100 has proven effective in two clinical standard mouse autoimmune models.
Collagen-Induced Arthritis
PRTX-100 has demonstrated reproducible efficacy in a well-established animal model of rheumatoid arthritis. Mice received two injections of collagen in order to stimulate an inflammatory response. One group was treated with various doses of PRTX-100, a second group received etanercept (Enbrel®), a leading commercially available treatment for rheumatoid arthritis, and the control group was injected with vehicle saline solution. The mice were observed for clinical symptoms, joint size and loss of function. The results showed that very low doses of PRTX-100 and standard doses of etanercept (Enbrel®) suppressed clinical symptoms, including joint swelling, over the first two to three weeks of treatment, and slowed disease progression as compared with the control group. Thereafter, the PRTX-100-treated mice continued to remain disease-free, whereas the mice treated with etanercept (Enbrel®) showed a resumption of joint inflammation and tissue damage. This response to etanercept (Enbrel®) was expected because the mice developed immune response to it because it is a foreign protein. Overall, these results indicate that PRTX-100 is a potential treatment for rheumatoid arthritis in humans. The data from these studies can be used as a rationale for conducting clinical trials in human patients.
BXSB Mice
These animals are genetically predisposed to autoimmune diseases. This model is therefore used to evaluate drugs for autoimmune diseases such as lupus, Crohn’s disease and others. This genetic model more closely approximates the human condition in that it is complex, multi-factorial and usually treated by multiple drug regimens. In these studies, mice were treated with PRTX-100 and sacrificed at regular intervals. Their organs were weighed and sectioned for histological analysis and their spleens were used for immunological assays. Spleen enlargement, or splenomegaly, was significantly reduced in treated animals compared with the controls at almost every time point, demonstrating the ability of PRTX-100 to delay the onset and severity of this disease. Treatment with PRTX-100 also reduced non-specific immunoglobulin production and specific autoantibody production and restored the number and function of immune cells (T and B cells). These results represent improvement in the context of an animal setting in this complex disease syndrome.
Completed pre-clinical safety studies in animals have shown no drug-related toxicity. In a safety study conducted in New Zealand white rabbits, all of the animals in this study survived to scheduled euthanasia. No differences were observed in body weight gain or food consumption, nor in hematology, clinical chemistry, urinalysis, or organ weight data in animals treated with PRTX-100 compared with controls treated with vehicle, or the same dilutive material, less PRTX-100. These data were a crucial component of the Company’s IND application with the FDA.
Additional studies in non-human primates to determine the pharmacokinetics of PRTX-100 have indicated more favorable dosing schedules. Since non-human primates are more closely related to humans, Protalex performed additional toxicology studies in monkeys to establish the toxicity and starting doses in humans.