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Here you can learn more about isotopic metallome, find our peer-reviewed publications, white papers, and third party research in support of our scientific stance, and many more...

Our Publications
Third Party (Oncology)
Third Party (Neurology)
Interesting
Our Publications
64Zn Aspartate Enhances Apoptosis in MB16 Cancer While Sparing Normal Cells

This white paper presents an evaluation of 64Zn-Asp cytotoxicity against MB16 and A-549 cells in vitro, assesses the 64Zn-Asp cancer-specific effects, and contemplates a hypothesis for 64Zn-Asp mechanism of action acting as isotope-selective PARP1 inhibitor. 

Anti-inflammatory Effects of 64Zn-Asp Accompanied by Cognitive Improvements in AD 

This peer-reviewed publication discusses our study for KLS-1 administration in rats with Aβ1-40-induced Alzheimer's disease (AD.) The article outlines our perspective on targeting systemic and neuroinflammation in AD and presents findings from our preclinical investigation in this area. The purpose of this study was to assess the effect of intravenous administration of novel investigational drug substance, 64Zn aspartate (KLS-1), on local and systemic inflammation and on cognitive parameters in rats with Aβ1-40-induced AD. 

Isotopically Modified 64Zinc Aspartate Renders Antimetastatic Effect In Vitro and In Vivo in Melanoma Cells

This paper reports the results of our study that explores the effects of an isotopically modified structural analogue of zinc-aspartate (64Zn-Asp) on the migratory and invasive activity of the malignant melanoma MB16 cells, in-vitro and in-vivo using an experimental hematogenous metastasis model in C57Bl/6 mice, and the expressions of Bcl-2, Bax, and p53 analyzed by immunocytochemistry. The activity of MMP-2 and MMP-9 was evaluated using the zymographic method. 

Therapeutic Potential of Isotopically Modified 64Zn Aspartate for Obesity Management

This peer-reviewed publication outlines our perspective on targeting obesity with the first-in-class, first-in-humans isotope selective modulator, KLS-1, and presents findings from our preclinical investigation in this indication. The purpose of this study was to assess the effect of 64Zn aspartate (KLS-1) on body mass, appetite, oxidative stress, and histopathological changes in pancreas and liver in Diet-Induced Obesity rodent model. The results show that KLS-1 slows down the development of obesity by 56% while improving the liver and pancreas functions.

Treatment With Isotopically Modified 64Zinc-Asp Alleviates Neuroinflammation and Motor Dysfunction in PD  

This paper outlines our perspective on targeting systemic inflammation in Parkinson's disease (PD) and presents our preclinical findings. The purpose of this study was to assess the effect of intravenous administration of novel investigational drug substance, 64Zn aspartate (KLS-1), on local and systemic inflammation and on cognitive parameters in rats with LPS-induced PD. 

First-in-Human Study of KLS-1 (64Zn L-Aspartate)

This publication presents the results of our small, non-registrational, first-in-human "learning" study of our KLS-1 drug candidate (64Zn enriched to >99%) in patients with oncological and neurodegenerative diseases. The purpose of this study was to establish initial dose of KLS1 for treatment of patients with various pathologies prior to conducting full-scale registrational Phase 1 clinical trial.

In Vitro Anticancer Activity of Light Stable Zinc Isotope (64Zn) Compounds

This peer-reviewed publication presents evaluation of cytotoxic activity of our first therapeutic drug candidate based of light zinc isotope 64Zn enriched to >99% against malignant MB16 melanoma and L1210 leukemia cells. 

Third Party (Oncology)
Zinc Dysregulation in Cancers and Its Potential As A Therapeutic Target

This review briefly summarizes the current understanding of zinc dyshomeostasis in cancer, and discusses the potential roles of zinc or zinc transporters in cancer therapy. The review is focused on isotopically natural zinc and does not discuss any possible isotope effects.

Investigations of Zinc Isotope Fractionation in Breast Cancer Tissue 

This review reports isotopic data for Zn uptake-efflux experiments using a human breast cancer cell line. MDA-MB-231 cell line was used as a model for triple receptor negative breast cancer. Zn isotopic composition in clinical samples of breast cancer tissue are analyzed relative to healthy tissue. 

Zinc isotope ratios of bones and teeth - Results from a modern food web

This reviereports the measurements of the ratio of stable isotopes of zinc (δ66Zn) in bioapatite (bone and dental enamel) of animals and demonstrates that δ66Zn values in both bone and enamel allow a clear distinction between carnivores and herbivores. 

The beneficial effect of zinc on low-dose chemotherapeutic sensitivity involves wtp53 activation in cancer cells

This review addresses that zinc supplementation might have a beneficial antitumor effect in wild-type p53-carrying cells in combination with other drugs, and that mutant p53 proteins undergo protein misfolding that can be counteracted by zinc.

Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets

This review consolidates the knowledge on the critical functions of cellular zinc signaling and underscores potential molecular pathways linking zinc metabolism to disease progression, with a special focus on cancer. The review also compiles a summary of clinical trials involving zinc ions.

Zinc chelation contributes to the anti-angiogenic effect of ellagic acid on inhibiting MMP-2 activity, cell migration and tube formation

The aim of this study was to investigate whether the zinc chelating activity of EA contributed to its anti-angiogenic effect.


Third Party (Neurology)

Inflammatory Hallmarks in 6-OHDA- and LPS-induced Parkinson's Disease in Rats

This publication presents a comparison of activation patterns of microglia/macrophage population and systemic inflammation indices in rats with 6-Hydroxydopamine (6-OHDA)- and Lipopolysaccharide (LPS)-induced animal models of Parkinson's Disease. This is essential for maximizing the translation of their potential to the clinic, as well as for developing putative anti-inflammatory neuroprotective agents.

A Review of the “Metallome” Within Neurons and Glia, as Revealed by Elemental Mapping of Brain Tissue

Systemic Inflammation in Aβ1-40-induced Alzheimer’s Disease Model: New Translational Opportunities

Neuroinflammation is associated with the impairment of blood–brain barrier and leakage of inflammatory mediators into the periphery with developing systemic inflammatory responses. Systemic inflammation is considered one of the therapeutic targets for AD treatment that necessitates in-depth study of this phenomenon in appropriate non-transgenic animal models. This publication discusses inflammation as one of the therapeutic targets for treatment of Alzheimer's disease (AD.)

A Review of the “Metallome” Within Neurons and Glia, as Revealed by Elemental Mapping of Brain Tissue

The aim of this mini-review is to present an overview of the current knowledge of the metallome found within specific brain cells (oligodendrocytes, astrocytes, microglia, and neurons), as revealed by direct elemental mapping techniques. Iron (Fe), Copper (Cu), and Zinc (Zn) are necessary for healthy brain function. Despite the known importance of metal ions for both brain health and disease, the metallome that exists within specific types of brain cells is yet to be fully characterised.

Interesting
You can grow new brain cells. Here's how | Sandrine Thuret | TED

In her TED Talk, neuroscientist Sandrine Thuret explains that adults can indeed grow new brain cells primarily in the hippocampus, a region crucial for learning, memory, mood, and emotion. She presents research showing that neurogenesis is linked to improved memory and mood, and that factors such as learning, physical activity (especially running), and certain dietary habits (like calorie restriction, intermittent fasting, and consuming foods rich in flavonoids and omega-3 fatty acids) can boost the production of new neurons. Conversely, stress, sleep deprivation, aging, high saturated fat intake, and excessive alcohol consumption can reduce neurogenesis. Thuret emphasizes that lifestyle choices can significantly influence brain health and encourages individuals to take charge of their neurogenesis to support cognitive function and emotional well-being as they age.

Stable Isotope Abundance and Fractionation in Human Diseases

The natural abundance of heavy stable isotopes is now of considerable importance in many research fields, including human physiology. In fact, it varies between tissues and metabolites due to isotope effects in biological processes, that is, isotope discriminations between heavy and light isotopic forms during enzyme or transporter activity. The metabolic deregulation associated with many diseases leads to alterations in metabolic fluxes, resulting in changes in isotope abundance. This review summarizes the current knowledge on changes in natural isotope composition in samples (including various tissues, hair, plasma, saliva) found in patients compared to controls, caused by human diseases.

Alternative Cancer Treatments & The New Biology of Water

In this interview, Dr. Cowan discusses his unconventional views on cancer and health, challenging mainstream medical assumptions by emphasizing the role of water biology in cellular health and disease, specifically the concept of "exclusion zone" water. He argues that cancer is not fundamentally a genetic disease, but rather a result of environmental toxins and disruptions in the body's water structure, suggesting that tumors act as the body's way of isolating and managing toxins, rather than being the primary disease itself. Dr. Cowan advocates for holistic cancer treatments that focus on detoxification, dietary changes (such as ketogenic diets and deuterium-depleted water), and minimizing exposure to environmental poisons and electromagnetic fields. He also questions the efficacy of conventional cancer screening and treatments, urging a reevaluation of basic biological assumptions and a greater focus on supporting the body's natural healing processes.

Costs of Drug Development and Research and Development Intensity in the US, 2000-2018

This economic evaluation study used data from public and proprietary sources to estimate the mean cost of developing a new drug from 2000 to 2018, which was $172.7 million (2018 dollars) but increased to $515.8 million when cost of failures was included and to $879.3 million when both drug development failure and capital costs were included. The ratio of R&D spending to total sales increased from 11.9% to 17.7% from 2008 to 2019.

For Life Without Parkinson’s Disease

The article profiles the groundbreaking work of Max Temnik, a chemistry PhD and entrepreneur, and Dr. Santosh Kesari, a leading neuro-oncologist, who are developing a potentially transformative, disease-modifying drug for Parkinson’s disease through their company, Metallomix Inc. (formerly Nomax Therapeutics). Temnik’s innovative approach centers on isotope-selective modulation of homeostasis (ISM), a process that targets the subatomic changes in human biomolecules associated with aging and disease. Preclinical studies in Parkinson’s-induced rodent models have shown that ISM treatment can prevent the degeneration of dopamine neurons and may even stimulate neurogenesis, offering hope for a true disease-modifying therapy. With encouraging safety results, the team is now seeking further investment to advance to full-size clinical trials, aiming to bring a therapy to market that could fundamentally alter the course of Parkinson’s disease and improve quality of life for millions worldwide.