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Could milk peptides treat central nervous system disorders?

By Francina Agosti | December 18, 2021

Milk

Image courtesy of Pexels

Scientists found milk components that may treat central nervous system (CNS) conditions, including anxiety and depression. These are new generation compounds that showed promising results in preclinical studies, predicting the avoidance of side effects caused by anxiolytics and antidepressants found in pharmacies.

Milk can indeed calm down many people — just think of the glasses of warm milk you had before going to bed and be able to get a good sleep after a hard day. But now, scientists went farther, and after examining milk components, they found peptides that could specifically treat anxiety and depression in clinical patients.

Using milk as a therapy

The use of milk for the treatment of diverse conditions is not new. Milk is a carrier of mother-to-young signals that are usually related to stress management and metabolic and developmental adaptations indispensable for the survival of the newborn. Harnessing those milk properties, many companies worldwide study specific components that can be beneficial for the health of humans.

One indicative example is the use of Lactium in dietary supplements. Lactium is a protein obtained from bovine milk hydrolysates after enzyme digestion. It’s a milk-derived mixture of ingredients that doesn’t cause any side effects. This product is used as a supplement to help with anxiety management, such as stress, sleep disorders, lack of concentration and more.

Based on the same idea that milk components help the newborn with stress management, Lactocore, a Massachusetts-based startup, decided to go even further and isolate individual milk peptides that could treat CNS disorders in a safe, direct and specific clinical setting.

Starting from Bos taurus milk hydrolysates, the Lactocore team used mass spectrometry to obtain individual peptides. “Regulatory peptides are found in milk of all mammals, and they are evolutionarily conserved (i.e., many of these signaling peptides are the same or have a similar structure in most species),” said Dr. Anton Malyshev, CEO and co-founder of Lactocore, predicting that cow’s milk peptides will be effective in humans. Later, they computationally converted the major peptides to tetrapeptides. “We focused our research on short peptides as candidate ligands because of their pristine safety and tolerability profiles for human therapies,” stated Dr. Malyshev. Once they identified a set of tetrapeptides, the scientists performed the docking with their in-house developed algorithm, Peptimize1. The docking consists of searching for peptides that (in silico) bind to the target proteins — in this case, neuronal proteins known to mediate anxiolytic effects of clinically successful drugs. After in vivo experimentation with the most promising tetrapeptides, Lactocore found that one of the candidates, codenamed LCGA-17, had the best potential to be developed as a drug for treating anxiety disorders2.

Benefits of new generation peptides against existent drugs

But why explore new drugs when there are already available ones for treating the very same conditions? The answer is simple: even if efficacious, clinically approved anxiolytics and antidepressants produce considerable side effects, including sedation and addiction.

Lactocore’s peptide, LCGA-17, is a new generation peptide tested in preclinical studies using zebrafish and rodents. The scientists found that LCGA-17 has anxiolytic and antidepressant-like characteristics in different behavioral tests applied to both species. Remarkably, LCGA-17 didn’t show sedative effects, and rodents didn’t develop addiction-like behaviors to the drug. Lactocore’s team believes LCGA-17 lacks toxic effects because it’s an easily degradable peptide naturally found in the milk that newborns obtain from their mothers. Clinical studies will tell more about its safety and efficacy in humans.

Lactocore is preparing the ground for planning the first-in-human clinical trials since promising preclinical studies showed that daily intranasal applications of LCGA-17 were safe and effective in rodent models of anxiety, depression, and even post-traumatic syndrome disorder (PTSD).

IT technology for the discovery of new peptides

Lactocore’s team is using their in-house docking technology, Peptimize1, to discover more peptides that could result in drug candidates. One case is the exploration for a short peptide to target a neuronal protein that modulates locomotor activity. Lactocore is currently performing preclinical studies on LCGM-10, a short peptide that might treat CNS-related locomotion disorders, such as Parkinson’s disease and dyskinesias. Future studies will define the specific use of LCGM-10 on clinical patients.

“When the need arose to apply computational approaches for prioritizing peptide candidates we have isolated, we were expecting that existing tools would easily solve this need. However, to our surprise, there were no good computational tools specifically tailored for peptide discovery, so we decided to first create several proprietary docking algorithms — Peptimize1 — and then an end-to-end peptide discovery engine altogether — Reptide — incorporating decades-worth of knowledge and experience of working with regulatory peptides, advanced structural biology and computational chemistry approaches and AI-powered modules,” said Dr. Malyshev. “We believe our recently generated IT platform Reptide could be exploited by companies in drug discovery phases, saving them time and money compared to in vivo experimentation.”

The future of milk components for CNS therapies

While these are only some examples, the use of milk peptides is a promising procedure to obtain non-toxic drug candidates for treating CNS disorders safely and effectively. Due to its inherent high safety, scientists believe these drug candidates could even be used by children, for example, as a therapy for attention deficit and hyperactivity disorder (ADHD). Clinical studies will tell more about these encouraging therapies and how to apply them to specific CNS disorders in humans. Meanwhile, did you drink your glass of milk today?

References

  1. A. O. Zalevsky et al., “PeptoGrid-Rescoring Function for AutoDock Vina to Identify New Bioactive Molecules from Short Peptide Libraries,” Molecules, vol. 24, no. 2, Jan. 2019, doi: 10.3390/MOLECULES24020277.
  2. A. V. Malyshev et al., “In silico Screening and Behavioral Validation of a Novel Peptide, LCGA-17, With Anxiolytic-Like Properties,” Front. Neurosci., vol. 15, Aug. 2021, doi: 10.3389/FNINS.2021.705590/FULL.

Francina Agosti, Ph.D., is a freelance science communicator. After working for ten years in academia in the neuroscience field, she started her own agency communicating science. She works with biopharma and biotech companies writing press releases and website articles, and designing deck presentations. Francina is a scientific editor for a non-profit association of cancer in pets, and she also writes health and science news for online magazines.

The opinions expressed in this article are the author’s only and do not necessarily reflect those of www.drugdiscoverytrends.com or its employees.


Filed Under: Drug Discovery, Neurological Disease
Tagged With: anxiety, depression, Lactium, Lactocore, milk
 

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