Many of us have experienced the challenges that come with chronic diseases such as cancer and kidney disease, either directly or as we support a friend or loved one. One challenge that is rarely talked about is cachexia. Cachexia, known as a “wasting syndrome,” can affect 50–80% of those with advanced cancers while adversely impacting quality of life and treatment outcomes. As such, it has always been a goal of research to solve cachexia – and now, innovative discoveries may turn into a major breakthrough that can finally make that happen and usher in a new era of cancer care.

Dr. Kenneth Gruber, founder, former CEO, and current Chief Scientific Officer of Endevica Bio, a company developing best-in-class peptide drug candidates with better safety and efficacy properties, answers these common questions about cachexia:

What Exactly is Cachexia?

The scientific definition of cachexia is defined as: a multi-organ hypermetabolic state, characterized by profound skeletal muscle and fat wasting in the context of a chronic inflammatory response. In basic terms, the body’s immune system triggers an imbalance in the hypothalamic melanocortin system, which is believed to be a central regulator of body mass, appetite, and energy.

I think that a good analogy is an automobile engine, which converts fuel into energy/movement. A car engine compresses the fuel with air in the cylinders and moves it to the pistons which ignite the air/fuel combination with a spark. There are times when an engine has a problem like the ability to maintain compression, which means that it’s essentially leaking energy, rather than using the energy for movement.

People with cachexia can eat food but converting that food/fuel to a common form of energy that all the cells in the body can use becomes faulty. is the energy from food is leaking out of the body, the way a malfunctioning car engine leaks energy and fails to work properly. In a car, if the engine problem causes it not to accelerate properly, you give it more gas by pressing the pedal, causing RPMs to go up, possibly into the redline.

In people who have cachexia and are leaking energy, the central nervous system tries to overcome this failure by increasing the metabolic rate., This produces a hypermetabolic condition – like getting into the red line with RPMs. When metabolic rate is too high, the body has become inefficient at converting food to energy and the cells can’t “work” properly. That’s why in many diseases, like cancer, there can be multi-organ failure even in organs that do not have tumors.

How is Cachexia Treated Today? 

Unfortunately, there are currently no pharmaceutical treatments that are specific for cachexia available in the United States. The American Society of Clinical Oncology (ASCO) does not recommend a specific pharmacological intervention, as there is not any evidence to support “claimed” treatments for cachexia.

Medical professionals often focus on trying to improve appetite or increase body weight, but these methods are unsatisfactory. It is important to remember that cachexia is not an appetite problem, it is a central nervous system issue. When someone has cancer, the immune system can activate areas in the central nervous system to increase the metabolic rate. So, in cachexia, it doesn’t matter how much food is ingested.

Back to the car analogy, if a car has a bad engine, the solution is not more gas in the tank. In cachexia, the body can’t properly use the fuel/calories it is given.

What Have Been the Challenges in Developing Cachexia Treatments?

One way that has potential to treat cachexia is to target the melanocortin system of the body. In very simple terms, the melanocortin system regulates how energy is used and it also has other functions, like determining skin pigmentation.

There have been two main challenges when developing melanocortin treatments. First, many treatments in development were found to have safety concerns, such as the risk of cardiovascular side effects. Second, the treatments needed to be formulated in a way so that they could safely cross the blood-brain barrier, in order to reach the central nervous system. Both of these challenges have been enormous hurdles, but the good news is that there’s promising research from experts, including myself, in peptide development that can overcome these issues.

What Treatments are on the Horizon?

One treatment that we are working on at the company I founded, Endevica Bio, is a drug called TCMCB07, a melanocortin antagonist peptide. We are excited about the potential of this treatment because so far in preclinical studies, it has crossed the blood-brain barrier, reduced inflammation in the brain and lowered the body’s metabolic rate so that it is able to use energy properly. We finished all of our preliminary studies and have filed our Investigational New Drug (IND) application with the U.S. FDA, which approved it. Currently, we are conducting a Phase 1 clinical trial in normal healthy volunteers. Based on the evidence we have gathered so far, along with our expertise in peptides and melanocortin antagonists, we believe we may have the best chance at finally combatting cachexia by solving it at the root of the problem. If we are successful, we believe we can help people that have cancer, along with other diseases where cachexia is common, improve their survival and quality of life.

Dr. Kenneth Gruber is the Founder, former CEO, and current Chief Scientific Officer of Endevica Bio. He is a former NIH Branch Chief and spent decades in academia as an NIH-funded investigator. He is the inventor on six patents (3 US & 3 EU) which protect the intellectual property used to develop TCMCB07, as well as other peptide therapeutics. He was the principal investigator on $4.5 million in NIH/NCI SBIR grants. These grants funded the development of the platform technology that produced TCMCB07, and the basic drug development research that demonstrated its small and large animal preliminary efficacy and safety.