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CACHEXIA
Confronting cachexia, the “wasting syndrome” seen in many cancer cases, may become easier with promising new drug development.

Late stages of a disease can often feel just as tumultuous as the earlier days in your journey. New symptoms pop up seemingly every other day, and it can become difficult to find relief and maintain a comfortable quality of life. But when it comes to cachexia, one of the most common and most harrowing disorders in late-stage cancer cases, some solace may finally be on the horizon.

Also known as “wasting syndrome,” cachexia is an irreversible disorder that occurs in advanced cases of cancer, kidney disease, heart failure, HIV/AIDS and more. It presents as loss of appetite on overdrive, causing the body to break down its own fat, muscle and even organs. Patients are typically diagnosed if there is a 5 percent loss of body weight over 12 months.

According to the American Cancer Society, up to 50 percent of all cancer patients may experience this disorder to a degree, leading to complications with treatment and well-being—and little opportunity for respite.

“At one time, cachexia was thought to be simply a disease produced by a lack of appetite in a small number of patients,” explains Dr. Kenneth Gruber, founder and chief scientific officer of biotech company Endevica Bio. Thanks to new research, however, the understanding of cachexia has evolved to recognize the large demographic it affects, the metabolic relation to cancer and its deadly outcome.

According to Gruber, up to 40 percent of cancer warriors will die from cachexia. Endevica Bio hopes to offset this number through the creation of a solution for the disorder based in peptides. Peptides are chains of amino acids held together by bonds within a cell; a well-known peptide therapeutic is insulin for diabetes. As Gruber notes, while the understanding of cachexia has deepened, the options available for patients with the disorder are still limited.

“There is currently no good drug treatment whose primary indication is to treat cachexia, which was the basis for Endevica Bio’s drug development efforts to produce an anti-cachexia therapeutic,” says Gruber. “Currently, health care professionals focus on maximizing nutrition and exercise in an attempt to limit weight loss and maintain muscle mass. The use of appetite stimulants and steroids are common, but these therapies don’t address the core problem—hence the high death rate.”

The core problem, Gruber says, is the hypermetabolic state of the body when faced with certain diseases. In cancer, metabolism may speed up—meaning a warrior already struggling with loss of appetite from disease or treatment will have a difficult time meeting the demands of a hyperactive metabolism.

To Endevica Bio, the answer lies within peptides, specifically melanocortins. These are peptide hormones within the neural system that are responsible for controlling body weight and other functions.

“The previous attempts to develop melanocortin drugs resulted in ones with cardiovascular side effects,” Gruber explains. “Endevica Bio has patents that can suppress these cardiovascular side effects while enhancing anti-cachexia effects. Many drugs are totally synthetic molecules that mimic natural peptides with potentially therapeutic activity.”

Endevica Bio’s peptide drug for cachexia has had promising milestones throughout its development. If approved, it would be administered as a daily injection. This is noteworthy in and of itself, as the properties of the drug would traditionally need to be administered directly into the brain’s cerebral ventricles to have any substantial effect on the melanocortin receptors—which is “clearly not practical and quite invasive,” Gruber points out.

The “drug-like” qualities of Endevica Bio’s treatment, which combines the low toxicity and high specificity of true peptides and long duration of synthetic molecules, allows a more straightforward and non-invasive approach that is ideally as effective. Once the melanocortin receptors are successfully blocked, a person with cachexia can begin gaining weight again—a feat virtually unheard of previously.

It might sound like a success story that’s too good to be true, but Endevica Bio has research funded by the National Cancer Institute to prove it. A veterinary hospital study of the drug in client-owned dogs with life-threatening cachexia showed “reversal of body weight loss, combined with reports of increased physical activity, and enhanced quality of life.”

There were also no drug-related adverse effects, and some dogs even continued on the drug for expanded use of over one year. Gruber says this has given the company confidence as the drug heads into human clinical trials.

While Endevica Bio’s primary focus is currently cancer cachexia, it hopes that any progress made with the drug in this demographic could also confront other cachexia forms such as those seen in kidney failure or heart failure. To Gruber, a change in the tide is fast approaching.

“Not only could [a cachexia treatment] potentially save many lives, but it could improve the quality of life of those who are living with cancer,” he says. “Similar to the new era ushered in by immunotherapies, we truly believe that if we can treat cachexia effectively it can be a major revolution in cancer treatment.”

Visit endevicabio.com for more information on the company’s cachexia research.

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