Stable Isotope Endpoints for Rare Disease & Gene Therapy

35+ Years exclusively in stable isotope tracer studies

Experimental protocol designs and results delivered weeks faster than CROs

GLP-compliant, CLIA-certified, 21 CFR Part 11 validated

Consultative approach, with over 1,000+ studies guided from design to submission

Stable isotope tracers provide direct, functional measures of enzyme activity. Below are examples of protocols used in rare disease and gene therapy trials, demonstrating how isotope assays translate therapeutic intervention into measurable biochemical endpoints.

Phenylketonuria (PKU) – ¹³C-phenylalanine breath test

Non-invasive breath test to assess phenylalanine hydroxylase (PAH) activity in PKU treatment and gene therapy trials.

Phenylketonuria (PKU) is a rare inherited disorder caused by a defect in the phenylalanine hydroxylase (PAH) gene, which leads to elevated phenylalanine levels in blood. A direct measure of PAH activity can be obtained using the stable isotope tracer [1-¹³C]phenylalanine, administered orally (Turki et al).

The ¹³C label on the carboxyl group of phenylalanine is metabolized and excreted as ¹³CO₂ in breath. Collecting breath samples provides a non-invasive method to monitor PAH activity following gene therapy aimed at restoring enzyme function.

This functional assessment of PAH activity, measured over a 60-minute period, serves as an endpoint for monitoring PKU treatment efficacy.

Methylmalonic Acidemia
(MMA – ¹³C-propionate breath test)

Breath test measuring MMUT enzyme activity to predict disease severity and monitor gene therapy response in MMA.

Methylmalonic acidemia (MMA) is caused by a defect in the gene coding for the mitochondrial enzyme methylmalonyl-CoA mutase (MMUT). This enzyme is essential for the oxidation of amino acids, odd-chain fatty acids, and cholesterol.

As reported by Manoli et al, propionate oxidative capacity, measured by the [1-¹³C]propionate breath test, predicts both disease severity and clinical outcomes in MMA. 

The ¹³C-propionate breath test provides a direct, functional measure of MMUT activity, making it a valuable endpoint to assess the therapeutic effects of genomic therapies for MMA

They’ve been very consistent… the sample analysis and data has always been timely and high quality.

There are academic labs that do it as well, but they’re much harder to engage and contract with.

I think they’re extremely organized and very on top of sample management. All the interactions that I’ve had with them have been great.

Stable isotope assays can quantify ureagenesis in urea cycle disorders (such as OTC deficiency), measure phenylalanine hydroxylase (PAH) activity in PKU, and assess propionate oxidation capacity in MMA. They can also be applied to fatty acid oxidation disorders, maple syrup urine disease, tyrosinemia, and galactosemia.

Tracer-based methods measure real-time metabolic flux. For example, ¹³C-acetate is incorporated into urea to reflect urea cycle function, ¹³C-phenylalanine is metabolized to ¹³CO₂ to reflect PAH activity, and ¹³C-propionate oxidation produces ¹³CO₂ to reflect MMUT function. These direct, functional measures demonstrate whether enzyme activity has been restored following treatment.

Endpoints can be measured using breath samples (e.g., ¹³C-phenylalanine or ¹³C-propionate tests) or plasma samples (e.g., ¹³C-acetate for ureagenesis). Both approaches are minimally invasive and practical across preclinical and clinical settings.

Metabolic Solutions, LLC.
460 Amherst St., Nashua,
NH 03063, USA

Phone: (603) 598-6960

Fax: (603) 598-6973

info@metsol.com

Hours of Operation
Monday – Friday
7:30 am – 6:00 pm EST

Metabolic Solutions offers a broad spectrum of assays utilizing stable isotopes such as carbon-13 (¹³C), nitrogen-15 (¹⁵N), deuterium (²H), and oxygen-18 (¹⁸O).

We have developed and validated non-invasive breath tests that assess sugar intolerances and gastrointestinal health.

Stable Isotope Assays for
Rare Disease & Gene Therapy Trials

What Sets Us Apart in Metabolic Biomarker Analysis

Tracer Protocols for Rare Disease & Gene Therapy Research

Phenylketonuria (PKU) – ¹³C-phenylalanine breath test

Methylmalonic Acidemia
(MMA – ¹³C-propionate breath test)

Other Rare Disease Endpoints utilizing Stable Isotope Breath Testing

All Analyses Are Performed In Our Certified Laboratory Environment

Trusted by Leaders in Metabolic Research

Frequently Asked Questions

Which rare disease endpoints can stable isotope tracers measure?

How do these tracer assays provide evidence of restored enzyme activity?

What sample types are required for these assays?

Let’s Turn Enzyme Activity into Evidence of Efficacy

Contact us

Research Services

GI Breath Tests

About Metabolic Solutions

Metabolic Solutions offers a broad spectrum of assays utilizing stable isotopes such as carbon-13 (13C), nitrogen-15 (15N), deuterium (2H), and oxygen-18 (18O).

We have developed and validated non-invasive breath tests that assess sugar intolerances and gastrointestinal health.

Stable Isotope Assays forRare Disease & Gene Therapy Trials

What Sets Us Apart in Metabolic Biomarker Analysis

Tracer Protocols for Rare Disease & Gene Therapy Research

Phenylketonuria (PKU) – 13C-phenylalanine breath test

Methylmalonic Acidemia(MMA – 13C-propionate breath test)

Other Rare Disease Endpoints utilizing Stable Isotope Breath Testing

All Analyses Are Performed In Our Certified Laboratory Environment

Trusted by Leaders in Metabolic Research

Frequently Asked Questions

Which rare disease endpoints can stable isotope tracers measure?

How do these tracer assays provide evidence of restored enzyme activity?

What sample types are required for these assays?

Let’s Turn Enzyme Activity into Evidence of Efficacy

Contact us

Research Services

GI Breath Tests

About Metabolic Solutions

Metabolic Solutions offers a broad spectrum of assays utilizing stable isotopes such as carbon-13 (¹³C), nitrogen-15 (¹⁵N), deuterium (²H), and oxygen-18 (¹⁸O).

Stable Isotope Assays for
Rare Disease & Gene Therapy Trials

Phenylketonuria (PKU) – ¹³C-phenylalanine breath test

Methylmalonic Acidemia
(MMA – ¹³C-propionate breath test)