Hypothesis: Oral administration of the oxalate metabolizing enzyme Oxazyme (OC4) will degrade food-borne oxalate and hence prevent its absorption from the gastrointestinal tract. In addition, by reducing oxalate concentrations in the gastrointestinal fluid, oxalate secretion from blood to the intestinal tract may be increased. Both effects would decrease blood levels of oxalate, and hence oxalate excretion in the urine.

开始日期2010-05-01

申办/合作机构

Mayo Clinic

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100 项与 Recombinant oxalate degrading enzyme(OxThera AB) 相关的临床结果

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100 项与 Recombinant oxalate degrading enzyme(OxThera AB) 相关的转化医学

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100 项与 Recombinant oxalate degrading enzyme(OxThera AB) 相关的专利（医药）

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项与 Recombinant oxalate degrading enzyme(OxThera AB) 相关的文献（医药）

2019-09-01·Journal of Immunology and Regenerative Medicine

Dendritic cells treated with exogenous indoleamine 2,3-dioxygenase maintain an immature phenotype and suppress antigen-specific T cell proliferation

Article

作者: Hassanzadeh, Azadeh ; Keselowsky, Benjamin G ; Brusko, Maigan A ; Bracho-Sanchez, Evelyn ; Wallet, Mark A

Indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme responsible for catalyzing the rate limiting step of tryptophan catabolism, plays a critical role in immune cell suppression and tolerance. Indoleamine 2,3-dioxygenase-mediated depletion of the essential amino acid tryptophan increases susceptibility of T cells to apoptosis, while kynurenine and its downstream metabolites, such as 3-hydroxyanthranilic acid and quinolinic acid, have a direct cytotoxic effect on conventional effector T cells. Additionally, IDO-expressing antigen presenting cells (APCs) induce proliferation of regulatory T cells. When expressed by an APC, the immunosuppressive effects of IDO may act directly on the APC as well as indirectly upon local T cells. One approach to elicit immune tolerance or reduce inflammation therefore is to promote expression of IDO. However, this approach is constrained by several factors including the potential for deleterious biologic effects of conventional IDO-inducing agents such as interferon gamma (IFNγ), and the potential limitations of constitutive gene transfection. Alternatively, direct action of recombinant IDO enzyme supplied exogenously as a potential therapeutic in the extracellular space has not been investigated previously, and is the focus of this work. Results indicate exogenous recombinant human IDO supplementation influences murine dendritic cell (DC) maturation and ability to suppress antigen specific T cell proliferation. Following treatment, DCs were refractory to maturation by LPS as defined by co-stimulatory molecule expression (CD80 and CD86) and major histocompatibility complex II (MHC-II) expression. Dendritic cells exhibited skewing toward an anti-inflammatory cytokine release profile, with reduced secretion of IL-12p70 and maintained basal level of secreted IL-10. Notably, IDO-treated DCs suppressed proliferation of ovalbumin (OVA) antigen-specific CD4⁺ and CD8⁺ T cells in the presence of cognate antigen presentation in a manner dependent on active enzyme, as introduction of IDO inhibitor 1-methyl-tryptophan, restored T cell proliferation. Defined media experiments indicate a cumulative role for both tryptophan depletion and kynurenine presence, in the suppressive programming of DCs. In sum, we report that exogenously supplied IDO maintains immunoregulatory function on DCs, suggesting that IDO may have potential as a therapeutic protein for suppressive programming with application toward inflammation and tolerance.

2013-03-01·Journal of Endourology3区 · 医学

Second Place: The Effects of Oxazyme on Oxalate Degradation: Results and Implications ofIn VitroExperiments

3区 · 医学

Article

作者: Holmes, Ross P. ; Knight, John ; Mufarrij, Patrick W. ; Assimos, Dean G. ; Lange, Jessica N.

Abstract Background and Purpose: Urinary oxalate excretion influences the development of calcium oxalate kidney stones. Urinary oxalate is derived from dietary sources and endogenous synthesis. Oxalate decarboxylase metabolizes oxalate and, if consumed, could theoretically accomplish this in the gastrointestinal tract. This study aimed to determine whether a commercially produced form of oxalate decarboxylase (Oxazyme(®)) could degrade oxalate in simulated gastric and intestinal environments.MATERIALS AND METHODSOne buffer (pH 3.6) simulated the gastric environment, while another (pH 6.5), approximated the proximal intestine. Potassium oxalate (soluble form of oxalate) and whole and homogenized spinach (a high oxalate containing food) were incubated in the different buffered solutions, with or without Oxazyme. Oxalate content, after incubation, was measured using established ion chromatographic techniques.RESULTSOxazyme resulted in complete degradation of oxalate derived from potassium oxalate in the intestinal buffer; meanwhile, oxalate derived from potassium oxalate in the gastric buffer was profoundly digested by Oxazyme. Adding Oxazyme also substantially reduced the oxalate content of both whole and homogenized spinach preparations, in either buffer.CONCLUSIONSThese in vitro findings demonstrate that Oxazyme can metabolize oxalate in both simulated gastric and small intestinal environments.

2010-01-01·International Journal of Toxicology4区 · 医学

14-Day Repeat-Dose Oral Toxicity Evaluation of Oxazyme in Rats and Dogs

4区 · 医学

Article

作者: Li, Qing-Shan ; Dean, Robin R. ; Sidhu, Harmeet ; Ghoddusi, Majid ; Poage, Duane W. ; Cowley, Aaron B. ; Meschter, Carol L.

Oxazyme (OC4) is an orally administered formulation that has as an active component a recombinant mutant form of Bacillus subtilis oxalate decarboxylase (OxDC) enzyme C383S, designed to degrade dietary oxalate in the stomach. Fourteen-day repeat-dose studies were conducted in rats and dogs to evaluate toxicity and determine a no observed adverse effect level (NOAEL). Animals were administered OC4 by oral gavage twice daily for 14 consecutive days. Reversibility, progression, and delayed appearance of any observed changes were evaluated in a subset of animals that underwent a recovery of 7 days following 14 days of control or test-article. There were no test-article-related adverse effects or deaths in either species. Results indicate that the NOAEL under the conditions used in the studies was 720.8 mg/kg/d in rats and 187.2 mg/kg/d in dogs, the high dose tested in each species.

100 项与 Recombinant oxalate degrading enzyme(OxThera AB) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
高草酸尿症	临床2期	-	OxThera AB	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01127087 (CTgov)	临床1/2期	高草酸尿症	22	Oxazyme (RYGB CaOx Stone Formers)	選構憲廠鏇餘鏇淵窪鹹(鬱積製艱襯築淵壓艱襯) = 範鹽醖廠簾網淵憲糧築衊選鏇窪窪製網憲網淵 (簾築衊壓網夢襯鹹襯憲, 範醖廠憲獵鹽構鏇顧壓 ~ 願獵齋憲艱鹽鹹鑰構憲) 更多	-	2012-12-24
				Oxazyme (Idiopathic Hyperoxaluria CaOx Stone Formers)	選構憲廠鏇餘鏇淵窪鹹(鬱積製艱襯築淵壓艱襯) = 鏇簾網觸鑰憲獵遞願觸衊選鏇窪窪製網憲網淵 (簾築衊壓網夢襯鹹襯憲, 鏇夢艱淵獵網廠獵壓鏇 ~ 顧顧襯夢廠憲範願醖簾) 更多