KALAMAZOO, MI, United States

Metabolic Solutions Development Co

www.msdrx.com
KALAMAZOO, MI, United States

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Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 121.96K | Year: 2014

? DESCRIPTION (provided by applicant): Polycystic kidney disease (PKD) is a term applied to a group of inherited disorders characterized by the presence of cysts in the kidney although multiple organs are typically affected. Renal pathologies found inessentially all forms of PKD include increased fluid secretion, matrix remodeling, cellular proliferation, and apoptosis, with a altered differentiation of the epithelial cells lining the renal cysts. PKD represent conditions tht are inherited as either autosomal dominant (AD) or autosomal recessive traits. ADPKD occurs in 1-in-500 to 1-in-1000 individuals, primarily as a result of mutations in one of two genes, PKD1 or PKD2. These mutations drive a pathology which results in inactivation of AMPK and over-activation of mTOR and Wnt signaling pathways leading to inappropriate cellular proliferation of the epithelial cells lining the tubules of the nephron. At this time, there is no therapeutic intervention approved for halting PKD progression. Metabolic Solut


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase II | Award Amount: 1.14M | Year: 2011

DESCRIPTION (provided by applicant): Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the United States. This condition encompasses both hepatic steatosis and the more severe non-alcoholic steatohepatitis. It is now estimated that 14-24% of the general population and up to 80% of morbidly obese subjects have contracted NAFLD. Untreated disease may progress to cirrhosis and lead to hepatic cancer. Cirrhosis now accounts for 12.5% of diabetes related deaths. In spite of the recognized need and degree of interest in the literature, there are no currently approved therapeutic agents for treatment of NAFLD and this unmet medical need will likely continue to increase in concert with the epidemic of obesity. The overall objective ofthe proposed research is to discover a PPAR?-sparing thiazolidinedione (TZD) which displays efficacy in a rodent model of non-alcoholic fatty liver disease (NAFLD) and demonstrates the necessary drug-like qualities to become a potential clinical candidatefor human therapeutics. The TZD class of insulin sensitizing agents are conventionally thought to operate through binding to PPAR? receptors. However, it is the strong contention of the authors of this proposal that the undesirable effects of the TZDs aremediated by binding to PPAR? receptors. Moreover, it has recently been suggested that rosiglitazone, the prototypical PPAR? activator, could exert untoward acute cardiovascular effects. Contrary to the prevailing scientific view, the authors of this proposal believe that non-PPAR mediated mechanisms are responsible for the insulin sensitizing pharmacology. The co-founders of the Metabolic Solutions Development Company (MSDC) have conceived of TZDs which should display minimal or no binding to the PPAR? receptor and has extensively evaluated their activity in cellular models (brown adipose precursor cell differentiation) and in rodent models of Type 2 diabetes. In Phase I studies, we evaluated a PPAR-sparing analog on a rodent model of NAFLD and the results clearly show that it improves insulin sensitivity accompanied by increased ability of the liver to oxidize and clear fat. Thus, the positive completion of this project provides an excellent foundation for selecting and developing a PPAR?- sparing TZD for treatment of NAFLD devoid of the side effects typically associated with this class of medications. The experimental work planned for Phase II would build on and extend this technology to achieve the selection and initial preclinical development of an analogfor treatment of NAFLD as well as the potential identification of a biomarker which could be useful for detection of early disease and to monitor therapeutic progress in clinical trials. PUBLIC HEALTH RELEVANCE: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the U.S. and the incidence of this disease has risen concomitantly with the epidemic of obesity. There is currently no approved therapeutic treatment for this liver disease. It is the overall goal of the proposed research to identify a candidate drug from the thiazolidinedione class which can be submitted to a development program for therapeutic use in treatment of NAFLD.


Patent
Metabolic Solutions Development Co | Date: 2014-09-05

The present invention provides novel methods for synthesizing PPAR sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases.


Patent
Metabolic Solutions Development Co | Date: 2015-08-05

The invention relates to Compound No. 1


The present invention relates to PPARy-sparing compounds and pharmaceutical compositions formulated with such compounds that are useful for treating, delaying the onset of, or reducing the symptoms of a neurodegenerative disorder including Huntingtons disease, epilepsy, AMS, and MS.


Patent
Metabolic Solutions Development Co | Date: 2014-07-21

The present invention relates to hydroxamate compounds and pharmaceutical compositions that are useful for treating and/or preventing metabolic inflammation mediated diseases such as diabetes, obesity, hypertension, dyslipidemia, a neurodegenerative disorder (e.g., Alzheimers disease, Parkinsons disease, or Huntingtons disease), or any combination thereof. Moreover, the present invention also provides methods of treatment for these diseases or disorders.


Patent
Metabolic Solutions Development Co | Date: 2013-01-28

The present invention relates to thiazolidinedione analogues that are useful for treating metabolic inflammation mediated diseases such as diabetes.


Patent
Metabolic Solutions Development Co | Date: 2013-09-20

The present invention provides novel methods for synthesizing PPAR sparing compounds, e.g., thiazolidinediones, that are useful for preventing and/or treating metabolic disorders such as diabetes, obesity, hypertension, and inflammatory diseases.


Patent
Metabolic Solutions Development Co | Date: 2014-10-30

The present invention relates to novel salts of thiazolidinediones and other pharmaceutical agents that are useful for treating and/or preventing metabolic diseases (e.g., diabetes, or neurodegenerative diseases (e.g., Alzheimers Disease).


Patent
Metabolic Solutions Development Co | Date: 2014-12-30

The present invention relates to thiazolidinedione analogues that are useful for treating metabolic inflammation mediated diseases such as diabetes.

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