Targeting TGF-beta growth factors to treat obesity

ABSTRACT The increasing rate of obesity has been declared and epidemic by the U SSurgeon GeneralIncrease obesity rates lead to an increase in related chronic diseases that have a profoundly negative impact on health worldwideThose include hypertensiontypediabetescardiovascular diseasesand cancersObesityrelated conditions cause an estimatedpremature deaths and cost overbillion dollars each year in the U SaloneGiven the strong link between obesity and serious co morbiditiesdeveloping safeand effective anti obesity treatments has become a global priorityCurrent approached to combat obesity focus on lifestyle changesweight loss surgeryand pharmaco therapyDietary and lifestyle changes can be effective but are difficult to maintain long termWeight loss surgery is only an option for treating adults and teenagers with severe obesity and related health problems such as typediabetesand high blood pressureMore importantlybariatric surgery is invasiveexpensive and associated with significant health risksMost FDA approved pharmacological approaches for treating obesity act on the brainby suppressing appetite or caloric intakeTableHoweverthese agents have a major history of failure due to adverse side effects and limited efficacyCurrent pharmacological approaches do not target the cellular process of producing adipose tissue or regulating fat storageThus revealing a critical need for effective pharmacological treatments that ameliorate or reverse the obese phenotype and improve obesity related co morbiditiesWe developed a novel protein based agentTLthat inhibits the Transforming Growth FactorTGFpathways with key roles in adipose tissue developmentturnoverhomeostasisor functionOur preliminary data shows that TLsuppresses new fat cell formation in culturereduces lipid accumulation in adipocytesand or prevents enlargement of fat depots in ovarectomizedOVXmice in vivoTlwas developed at Michigan State University in the laboratory of DrErik Martinez HackertTalapo Therapeutics has obtained an exclusive license to a published patent from Michigan State Universityand for two follow up applications that will be filed in the near futureTo evaluate our novel anti obesity therapeuticwe propose the following Specific AimsAIMDefine role of Talapo agents on body composition and metabolism of mice subjected to high fat dietHFDAIMDetermine safety profile of TLAIMValidation of TLin human pre adipocyte differentiation and identification of biomarkersSuccessful completion of this project will demonstrate that TLreduces fat deposits in two different animal modelsThis will lay the foundation for a Phase II study and further therapeutic development NARRATIVE Obesity is a growing problem worldwide and the obesity related conditions cause an estimatedpremature deaths per yearWe have developed four novel agents that reduce fat depots in a preclinical model of obesityThis project will solidify the fat reducing action of Talapo agents in two preclinical models of obesity