Hypomagnesemia is an electrolyte disorder of low serum magnesium <0.7 mmol/L; often caused by some genetic defects of the kidneys which hinder the reabsorption of magnesium. Protheragen offers comprehensive preclinical services focusing on novel therapies for refractory hypomagnesemia, with particular emphasis on rare tubular transport disorders.
Introduction to Hypomagnesemia
Hypomagnesemia describes lower serum magnesium levels with a cut off of 0.7mM (1.7 mg/dL). It is often secondary to medication, nutritional, or gastrointestinal factors, but sometimes it stems from a genetic disorder. Outpatient cases of hypomagnesemia are mild, but it is much more common in the inpatient population. Rougly, hypomagnesemia impacts cellular function in neuromuscular systems and cardiac rhythm, and it is often accompanied by hypokalemia and hypocalcemia. It is very reliant on renal function alongside malfunctioning kidneys, signaling a greater need for research on the underlying mechanisms and more precise treatments.
Pathogenesis of Hypomagnesemia
Diverse mechanisms of hypomagnesemia include insufficient magnesium intake, altered intracellular distribution of magnesium, excessive magnesium loss, and change in intracellular distribution. A major contributor within the inherited forms of the condition is renal magnesium wasting.
Fig.1 Schematic drawing of Mg
2+ reabsorption by different segments of the nephron. (Claverie-Martin, Perdomo-Ramirez and Garcia-Nieto, 2021)
The regulation of magnesium balance in the body is important, and the kidneys achieve balance by reabsorbing nearly 96% of magnesium along the nephron. Key sites for the reabsorption of magnesium are the thick ascending limb of Henle's loop and the distal convoluted tubule. Additionally, some diseases and drugs can cause inappropriate magnesium wasting by the kidneys. Genetic forms of hypomagnesemia are usually associated with pathogenic variants of genes for magnesium transport proteins causing deficient reabsorption in particular tubular segments and therefore lead to renal magnesium wasting. Inflammation and fibrosis in the tubules can be caused by other forms of chronic hypomagnesemia, which can persistently injure kidney tubules, and this condition can be linked to chronic kidney disease.
Therapeutics Development for Hypomagnesemia
| Therapeutic Strategy |
Therapeutic Target |
Key Mechanisms/Advances |
Development Stage |
| Hydrogel-based sustained release |
Intestinal Claudin-12 tight junction protein |
Alginate-chitosan hydrogel upregulates Claudin-12 expression, enhancing paracellular Mg2+ flux
• Serum Mg2+ increase: +0.1 mmol/L (72h) in Phase II |
Phase II |
| LNP-delivered TRPM6 modulators |
TRPM6 kinase domain (S1411-L1850) |
Allosteric agonists bind TRPM6-specific hydrophobic pocket, increasing channel open probability by 300%
• Tissue specificity: <5% hepatic/renal distribution |
Preclinical |
| CRISPRa-TRPM6 activation |
TRPM6 promoter estrogen response element (ERE) |
dCas9-p300 acetylates H3K27 at -956 to -943 bp ERE site, reversing epigenetic silencing
• Organoid efficacy: TRPM6 expression increases 3-fold |
Preclinical |
| Liver-targeted sTRPM6 therapy |
Soluble TRPM6 ectodomain (amino acids 1-480) |
AAV8-expressed truncated TRPM6 binds renal BSND protein, activating endogenous TRPM6
• Sustained correction: >6 months in CNNM2-mutant models |
Preclinical |
| Anti-FGF23 monoclonal antibody |
FGF23 C-terminal Klotho-binding domain (K180-P251) |
Humanized IgG blocks FGF23-Klotho interaction, inhibiting Wnt/β-catenin signaling
• Reverses vitamin D resistance in CKD models |
Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen offers specialized services in developing advanced disease models for hypomagnesemia, complemented by comprehensive preclinical therapeutic development. Our efforts are dedicated to deciphering the complex genetic and physiological factors that underpin this electrolyte imbalance and its associated renal complications.
Therapeutic Development Platforms for Hypomagnesemia
Disease Models Development for Hypomagnesemia
Protheragen offers innovative and comprehensive disease models to advance the preclinical research of hypomagnesemia. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the ciliary dysfunction and developmental defects that cause hypomagnesemia.
- TRPM6V1393M mutant DCT cells
- CLDN16L145P TAL epithelia
- FXYD2G41R collecting duct cells
- DCT-specific TRPM6-deficient organoids
- Pressure-sensitized nephron chips
- Trpm6Y295C knock-in mice
- Cldn16del/del zebrafish
- Fxyd2G41R transgenic rats
- Inducible CNNM2 knockout rabbits
- Humanized SLC41A1 mutant mice
Drug Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Renal Clearance Assay
- Drug-Transporter Interaction Screening
- Metabolic Stability Assay
- CYP Inhibition Screening
- Plasma Protein Binding
Protheragen provides integrated preclinical development solutions specifically designed for kidney research, including conditions like hypomagnesemia. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation.
Contact us today to accelerate your hypomagnesemia research with end-to-end solutions.
References
- Claverie-Martin, F., A. Perdomo-Ramirez, and V. Garcia-Nieto. "Hereditary Kidney Diseases Associated with Hypomagnesemia." Kidney Res Clin Pract 40.4 (2021): 512-26.
- Salinas, M., et al. "Improving Diagnosis and Treatment of Hypomagnesemia." Clin Chem Lab Med 62.2 (2024): 234-48.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
