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San Diego, CA, United States

Patent
Zacharon Pharmaceuticals Inc. | Date: 2010-03-29

Provided herein are ganglioside synthesis inhibitors, including modulators of ganglioside glycosylation.


Patent
Zacharon Pharmaceuticals Inc. | Date: 2012-09-27

Provided herein are methods of diagnosing or monitoring the treatment of abnormal glycan accumulation or a disorder associated with abnormal glycan accumulation.


Patent
Zacharon Pharmaceuticals Inc. | Date: 2012-07-16

Provided herein are methods of diagnosing or monitoring the treatment of abnormal glycan accumulation or a disorder associated with abnormal glycan accumulation.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 335.74K | Year: 2012

DESCRIPTION (provided by applicant): The goal of this proposal is to develop a biomarker capable of definitively diagnosing and monitoring response to therapy in patients with Mucopolysaccharidosis (MPS) I, II and VI. These diseases are rare genetic conditions each caused by unique deficiencies in the lysosomal enzymes required for the degradation of glycosaminoglycans (GAGs). The resulting lysosomal accumulation of GAG fragments leads to severe physical, developmental, and neurological symptoms with dramatic heterogeneity between different patients. Since lysosomal GAG accumulation is the primary cellular event triggered by the lysosomal enzyme deficiency, the measurement of GAGs is an ideal biomarker of the disease. Unfortunately, prior attempts to quantify GAG accumulation have been unsuccessful due to the extremely variable polymer length and sulfation and significant background from non-pathogenic GAGs that are normally present in biological samples. The Sensi- Pro method solves this problem using an innovative approach to quantify the unique GAG structures that arise due to the specific lysosomal defect. Because each MPS disorder is deficient in a distinct lysosomal degradative enzyme, the Sensi-Pro biomarkers are discrete for each MPS disorder and are not found in unaffected people. The Sensi-Pro assay has demonstrated the ability to quickly and accurately differentiate the various MPS disorders in addition to the ability to monitor individual patient responses to the FDA approved therapies. This proposal aims to develop the Sensi-Pro assay further for clinical use for the differential diagnosis and measurement of response to therapy in MPS I, II and VI. This will be accomplished through a series of studies in collaboration with ARUP Laboratories designedto establish the standards for the MPS I, II, and VI biomarkers, multiplex the assay, and validate the assay in a CLIA compliant environment. With the multiplexed assay established, it will be tested for the ability to differentiate between MPS disordersand detect a response to therapy in samples from a clinical trial for MPS I. Upon successful completion, the assay will be commercialized by ARUP Laboratories as a clinical assay for the definitive identification of MPS patients and optimization of treatment protocols. PUBLIC HEALTH RELEVANCE: This research is designed to develop a novel biomarker for the definitive diagnosis and clinical management of patients with Mucopolysaccharidosis I, II, and VI. These diseases are rare genetic conditions caused by defects in the cellular systems required to degrade carbohydrates. The successful conclusion of this research will provide a critical diagnostic tool enabling the identification of affected patients, selection of appropriate therapy, and optimization of treatment strategies.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 296.24K | Year: 2012

DESCRIPTION (provided by applicant): The objective of this Phase I SBIR proposal is to develop a central nervous system penetrant (CNS) small molecule therapy for Metachromatic Leukodystrophy (MLD). We will accomplish this by developing a cellular model ofMLD to screen compound libraries in order to identify small molecule screening hits suitable for lead optimization to develop drugs for the treatment of this devastating disease. MLD is a rare genetic condition found in 1 in 40,000 births that is caused by a deficiency in the lysosomal arylsulfatase A (ASA) or saposin B (SAPB) [1, 2]. The lack of ASA activity leads to widespread accumulation of 3-O sulfated glycolipids in the lysosomes of cells. The accumulation of sulfated glycolipids in oligodendrocytesand neurons in the CNS leads to the profound neurological deterioration and ultimately death. In this proposal, we aim to change this situation by developing a model of MLD based on cells from patients with MLD. This assay will enable the high throughput screening of compound libraries in order to identify novel treatments for this destructive disease. To accomplish this, we propose to develop rapid analytical method for the quantitation of the primary 3-O sulfated glycolipid (sulfatide) that accumulates incultured human MLD cells. This assay will be used to screen compound libraries for inhibitors of lysosomal sulfatide storage. Finally, the hits will be prioritized based on their mechanisms, potency, ADME, and PK properties. Upon successful completion ofthis proposal, we will have identified the hit compounds that can serve as the starting point for the discovery and development of a novel CNS penetrant therapy for MLD. PUBLIC HEALTH RELEVANCE: This research is designed to identify a treatmentfor Metachromatic Leukodystrophy, a genetic condition that causes severe neurological disease. There are currently no effective therapeutic options for this life threatening disease. If successful, this research could lead to a therapy for Metachromatic Leukodystrophy.

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