According to The World Health Organization 2016 fact sheet, an estimated 350 million people of all ages suffer from depression globally. Depression is the leading cause of disability worldwide and a major contributor to the overall global burden of disease. The condition can detrimentally affect a person’s ability to work, have relationships, and destroy their quality of life.
What We Don’t Know: The Causes Of Depression
While science has made gigantic strides towards unraveling the mysteries of the brain, we still don’t know for sure how depression works or what’s a cause and what’s a symptom even. Attributing depression to neurochemical levels, the monoamine theory, has been the predominant thinking for decades. In the 1960s, we were told depression was due to insufficient norepinephrine. Then, a still popular theory blamed depression on too little serotonin. Today, we know that it’s much more complicated than either of these and involves many other neurochemicals which influence and are influenced by depression.
Big Pharma has played a major role in keeping this idea alive. Antidepressant drugs, based on the monoamine theory, accounted for a $9.4 billion dollar market in the U.S. alone in 2013. According to the Scientific American article, The Rise of All-Purpose Antidepressants, adults in the U.S. consumed four times more antidepressants in the late 2000s than they did in the early 1990s – despite evidence showing little benefit.
According to a report published in The Journal of the American Medical Association (JAMA), antidepressants work best for very severe cases of depression and have little or no benefit over a placebo in less serious cases.
An alternative explanation for depression gaining popularity is the cytokine theory which proposes that depression isn’t a disease itself at all, but a body’s inflammatory response to stress. The latest research is suggesting that depression is associated with chronic inflammation, attributed primarily to influenceable lifestyle factors, like diet, stress, sleep, physical activity, and dental and gut health.
What We Do Know
In What Depression Looks Like In your Brain, I explain:
Fundamentally, a depressed brain looks just like any other brain. At the most basic level, depression is just the routine activation of certain brain circuits, which we all have, in specific patterns that result in depressive symptoms in a person.
We all have the same basic brain structure although the neuronal connections, determining the activation of and communication between brain circuits, are unique to every person. The particular circuits excited over and over in your brain become the go-to default pattern for you and are the product of your thoughts, interactions with others and the world, and the events that happen to you.
So, depression is the product of specific patterns of activated circuits in your brain and how they interact and impact each other. We know that there are factors which contribute to forming depressive patterns in a brain, including genetics, early childhood, life events, stress, and social support.
A Different Approach
There is an approach to treating depression that has shown promise by interrupting the melanocortin system. Melanocortins are signals released in the brain in response to stress. Studies with rodents suggest that blocking the melanocortin signal successfully relieves depression and anxiety without harsh side effects in a fraction of the time.
Melanocortin-releasing neurons stretch out of the brain’s hypothalamus to make contact and communicate with other brain regions that control emotional states. Research with animals suggests that overactive melanocortin neurons contribute to hyper-emotional states and that slowing the release of melanocortins reduces depression.
The official name of the first drug developed for depression acting on the melanocortin system was melanocyte-stimulating hormone release-inhibiting factor 1 (MIF1). MIF1 was shown to contribute to the brain’s natural way of inhibiting melanocortin release and is a molecule naturally produced in the brain. Naturally occurring molecules are difficult, if not impossible, to patent. For the drug companies, no patent equals no money.
Scientists whipped up something similar to MIF1, Nemifitide, which could be patented. Nemifitide made it to phase II clinical trials, a huge step toward FDA approval, and it wildly outperformed antidepressants. When people were treated with Nemifitide for just five days, most of the depressive symptoms were gone in most of the people for an average of 3-4 months.
Why haven’t you heard of Nemifitide? By the time the small company developing the drug got past all the business and regulatory hurdles, they only had four years remaining on their patent. When a drug loses its patent protection, generic drug makers flood the market with less expensive knock-offs. For huge conglomerate drug companies with huge sales forces and marketing expenses, the investment wasn’t worth the potential gain.
Resurrecting The Super Depression Drug
Dr. Caurnel Morgan, PhD, began investigating the role of the melanocortin system in mouse models of depression and anxiety in 2001. Specifically, he studied a particular component of the melanocortin system – the melanocortin-5 receptor (MC5R). With promising results and the aid of colleagues, Dr. Morgan’s work evolved to develop and center on MC5R blockers. In studies with mice, MC5R blockers were three times more effective than antidepressants and worked one thousand times faster.
In April of 2016, Akhu Therapeutics headed by Dr. Morgan, acquired a worldwide license for a series of peptide compounds designed to block the melanocortin-5 receptor (MC5R) to develop them to treat depression and anxiety. The press release quoted Dr. Morgan:
Our expectation is that this technology will help depressed and anxious people within hours as opposed to having to wait weeks for a therapy to work. We also expect that it will lack some of the side effects that are associated with current drug therapies.
In an interview, Dr. Morgan expressed:
Melanocortin blockers have consistently beat antidepressants in effectiveness and speed in studies of depressed people and animal models, but, they’ve been difficult to protect with patents – until now. Our next-generation melanocortin blockers are effective and fast in animal models, and protected by 9 patent applications. We’re raising funds to complete the research necessary for FDA approval to use them in people.
Akhu Therapeutics has an IndieGoGo campaign, with the slogan “Making the best damn medicine for anxiety and depression!”, to help raise the funds to complete the research necessary to bring this technology to the public. Donations can be as little as ten dollars. Go here to help “Extinguish Anxiety and Depression.”