Lactocore Group is a privately funded company with a team of biologists, biochemists and computational biologists (10 PhDs) exploring transformative new medicines derived from milk peptides for treatment of mental and metabolic diseases.
Lactocore’s expertise in silico drug discovery, peptide drug development, and behavioral neuroscience. A lean, efficient, semi-virtual company, Lactocore has its HQ in Massachusetts and a network of global Clinical Research Organizations and collaborators. The combination of proprietary computational tools and a lean international team allows conducting cutting-edge R&D at a fraction of the cost of traditional biotech companies.
We asked Dr. Anton Malyshev, CEO of Lactocore, some questions about the therapeutic potential of milk peptides.
GD: To begin, please explain what a peptide is.
A peptide is a very small protein. It consists of several amino acids and usually has only a primary, less often also a secondary structure. The bottom line is that this set of amino acids makes up a molecule that has its own action. For example, it can activate or inhibit certain receptors on cells. Some peptides are more like neurotransmitters in their mechanism, others are more like hormones. Peptidergic regulation in the human body is quite diverse and extremely important. It is also curious to note that there are both endogenous (i.e., produced in the human body) and exogenous (coming from outside, for example, with food) peptides.
GD: What led you to explore milk peptides as a possible source of new drug compounds?
It was based on a scientific curiosity in the regulation of infant-maternal interactions. Milk is an essential and primary source of nutrition for the infants of all mammals. And in addition to its nutritional value, it has a regulatory value – specifically through those exogenous regulatory peptides. These peptides have an impact on the development of the nervous system and can regulate emotions and behavior of the infant. There is a large variety of peptides in milk, so we tried to find new peptides, unknown until now, that have some kind of regulatory value. We stepped aside from the concept of functional nutrition and started making these peptides pharmaceutically acceptable in order to turn them into drugs that anyone, not only children, would be able to use. Later on we even moved further from the original source of the peptides, the milk, and made an IT platform using structural bioinformatics approaches to generate molecules “de novo” for given molecular targets and pathological mechanisms.
GD: I understand you are focused on a particular peptide, called LCGA-17. What is its potential?
At the moment there are three main areas in our pipeline: mental illness; metabolic disorders; age-associated cognitive problems. LCGA-17 is our leading molecule in the stress-related field. According to a large number of preclinical animal studies, we know that this molecule has powerful antianxiety and antidepressant effects. It is important that this effect has a rapid sense of action quickly and lasts for a long time, which is very useful for patients with anxiety-depressive diseases. At the same time, LCGA-17 has a very clean safety profile, causing no sedation, drowsiness, addiction or other typical side effects of psychiatric drugs.
GD: Are there other peptides that you are researching further?
In our metabolic research, the molecule CHM-273s is leading the way. It is also a short regulatory peptide that lowers blood glucose levels and has great potential for the treatment of type 2 diabetes and the obesity. At the same time, this peptide also has a central element in its mechanism of action: it reduces appetite and helps regulate eating behavior in both acute and chronic applications. Like LCGA-17, it is very safe. We are also working on a patient-friendly drug product – a nasal spray that only has to be used once a day.
GD: There have been drugs on the market for decades to treat anxiety and depression. How would drugs derived from milk peptides differ?
The first key difference that comes to mind is the safety of peptides. Unfortunately, 91% of the registered drugs have more than 10 documented and clinically observed side effects. This can be partly attributed to the fact that they are made on the basis of small molecules, which are metabolized by our body to a limited extent. The peptides, on the other hand, are recognized by human enzymes without any problems and are decomposed into amino acids, which are either easily eliminated from the body or integrated into the energy cycles of the cell. This is probably an interesting evolutionary mechanism. Meanwhile, of course, we always make sure that the efficiency of our peptides is as good as, and often better than, known standards of comparable drugs.
GD: LCGA-17 has been tested in preclinical studies using zebrafish and rodents. What were the results? Are human trials planned?
Yes, that’s absolutely right: we’ve conducted a large number of studies in various animal models. We use fish in the first stage for initial screening for the activity of a large number of compounds. On rodents, rats and mice, we do more complex models that correspond to a particular human disease. For example, we simulated a depressive-like behavior in rodents using an unpredictable chronic stress protocol. In this paradigm, animals are exposed to random and unavoidable, but not too harsh, stressors for 2 months. As a result, typical behavior of despair and anhedonia is formed, which LCGA-17 successfully relieved. Another curious pattern is the acute stress model using a very strong natural stressor for all rodents, the scent of a predator. Presenting this stimulus produced PTSD-like behavior in the animals. LCGA-17 was effective in this case as well, and it resulted in a reduction of the sense of fear when the animals realized that there was no real threat, rather than in a total oblivion of the experience. For CHM-273s we modeled a high-fat diet: we used special laboratory food for mice with a high fat content. After six months, the animals developed obesity and a diabetic-like condition. Chronic intranasal injections of CHM-273s resulted in normalization of blood glucose levels, loss of 30% of excess body weight, and reduction of proinflammatory cytokine levels to control values.
