Long-acting ghrelin for the treatment of cancer cachexia

Project Summary Cachexia is a complex syndrome characterized by involuntary weight loss and skeletal muscle wasting that leads to fatigueweakness and a loss of appetite that is not reversed by increased caloric consumptionMore than half of all cancer patients develop cachexia and it is responsible for more thanof all cancer deathsNumerous complications associated with cachexia include an impaired response to drug treatmentan increased chance of infectiona poor prognosis and a decreased quality of lifeCurrentlythere are no FDAapproved treatments for cancer cachexiabut the hormone ghrelin has recently emerged as a molecule with great potentialSeveral studies in both animals and humans have shown that ghrelin increases food intakestimulates the release of growth hormoneincreases muscle massand reduces markers of inflammationHoweverthe use of ghrelin as a treatment is limited for several reasonsghrelin must be dosedtimes daily to see efficacy due to its inherently short half life ofmindeacylation of ghrelin to an inactive form occurs in less thanminandghrelin is currently dosed intravenously to see a therapeutic effectThe studies completed during SBIR Phase I address each of these issuesresulting a long acting ghrelin derivative that could be dosed subcutaneously once every other day in rats to reverse the effects of cachexia in the Yoshida rat modelThe studies proposed in this Phase II application will investigate the ability of our longacting ghrelin to ameliorate cachexia in two additional modelsMethods for cGMP production of the long acting ghrelin will be put in placeWe will perform IND enabling GLP toxicity and immunogenicity studies using the cGMP materialThese studies are needed prior to beginning human trialsOnce fully developedthis longacting ghrelin derivative would provide a patient friendly cachexia therapy that would significantly improve the prognosis and quality of life in patients with cancer and also in patients with other chronic disorders such as congestive heart failureCHFand chronic obstructive pulmonary diseaseCOPDProject Narrative Cancer is often coupled with a serious condition called cachexia or involuntary weight lossStudies have shown that cancer patients who have cachexia often respond poorly to chemotherapyare at a greater risk of infection and have a reduced life expectancyCurrently there is no effective way to treat cachexiaThe work described in this proposal will help develop treatments for cachexia based on a hormone made by the body that increases appetite and stimulates muscle growthRelieving the symptoms of cachexia will significantly improve a cancer patientandapos s quality of life and decrease the need for hospitalizationsresulting in reduced healthcare costs