Rhodase is potentially a safer and more effective novel treatment for Acute Lymphoblastic Leukemia. Rhodase is L-asparaginase from Gram-positive R. rhodochrous. The R. rhodochrous bacterium is ubiquitous in soils. R. rhodochrous does not contribute to any pathogenesis and is capable of using a wide range of organic compounds as sole sources of carbon and energy to support growth.
Acute lymphoblastic leukemia (ALL) – is the most prevalent form of childhood cancer. ALL accounts for 80% of leukemia cases diagnosed in children under age 5. Nearly 88% of children who complete the treatment with asparaginase experience 10 years leukemia-free. There is a 94% overall survival at 10 years. Patients who complete all doses of Asparaginase treatments have better outcomes and lower rates of recurrence than those who do not.
The current standard treatment for ALL in juvenile many adult protocols is Asparaginase therapy (with or without chemotherapy). Acute lymphoblastic leukemia cells lack the ability to synthesize the amino acid L- asparagine. When a patient has ALL, leukemia cells cannot make L- asparagine and are forced to obtain it from the host bloodstream. Depletion of asparagine and the inability to synthesize protein leads to cell death.
Since the discovery of the utility of asparaginase and the commercialization of the E. coli and Erwinia enzymes, the literature is filled with reports of enzyme sources in a wide range of microorganisms. Most of these studies are based on only small volumes of culture and the feasibility of scale up to commercial levels is challenging. Our technology has demonstrated that scale up to over-produce quantities of very active stable enzyme preparations is reasonable.
Current L-asparaginase treatments, whether native or modified by pegylation, come from Gram-negative bacteria such as E. coli and Erwinia chrysanthemi. L-asparaginase from Gram-negative bacteria contain immune-stimulating factors. Gram-negative bacteria have outer cell walls coated with lipopolysaccharides with endotoxins that trigger a powerful immune response. Even very low concentrations of lipopolysaccharides are enough to stimulate the body’s innate and adaptive immune system. Gram-positive cells do not have lipopolysaccharides. The current clinical protocol is to switch patients to a different type of L-asparaginase during an allergic reaction.
When L-asparaginase triggers allergic reactions the dosing must be reduced or discontinued. Common L-asparaginase toxicities are: Serum sickness, Cerebral dysfunction, Pancreatitis, Elevated hepatic enzymes, Decreased protein synthesis, Thrombosis, Hypoalbuminemia, Hyperglycemia, Hypersensitivity, Anaphylaxis.
Patients treated with L-asparaginase that do not develop serious allergic reactions often develop rapid drug resistance as the body produces neutralizing antibodies to foreign protein. The specific mode of resistance has not been fully characterized. The phenomenon is known as “silent inactivation.”