What side effects are associated with this type of intervention?

The most common treatments for Propionic Acidemia include dietary management, carnitine supplementation, and emerging mRNA therapies like mRNA-3927. mRNA therapies can cause immune reactions, injection site reactions, and potential off-target effects. Dietary management may lead to nutrient deficiencies and gastrointestinal discomfort, while carnitine supplementation can also cause gastrointestinal issues. It is important to discuss these potential side effects with a healthcare provider to tailor the treatment plan to the patient's needs.

What prior FDA approvals exist?

As of now, there are no FDA-approved mRNA therapies specifically for the treatment of Propionic Acidemia. Traditional treatments for Propionic Acidemia primarily focus on dietary management, carnitine supplementation, and in some cases, liver transplantation. The mRNA-3927 trial represents a novel approach by using mRNA therapy to produce functional proteins that are deficient in individuals with Propionic Acidemia, aiming to address the underlying genetic cause of the disorder.

What other types of research exist?

Promising novel alternatives to mRNA-3927 for Propionic Acidemia patients include gene therapy approaches that aim to correct the genetic defect causing the enzyme deficiency, and enzyme replacement therapies that provide the functional enzyme directly. These therapies are in various stages of research and development and may offer new hope for PA patients in the near future.

← Back to Search

RNA Therapy

mRNA-3927 for Propionic Acidemia

Q: What is the mechanism of action of this treatment?

Propionic Acidemia (PA) is a metabolic disorder caused by deficiencies in the enzymes propionyl-CoA carboxylase, leading to the accumulation of toxic metabolites. Traditional treatments include dietary management to limit the intake of certain amino acids and odd-chain fatty acids, and the use of medications like carnitine to help remove toxic compounds. mRNA therapy, such as the mRNA-3927 trial, aims to introduce functional mRNA into the patient's cells to produce the deficient enzymes. This approach directly addresses the root cause of PA by enabling the body to produce the necessary enzymes to metabolize propionyl-CoA properly, potentially reducing the accumulation of toxic metabolites and improving metabolic stability. This is crucial for PA patients as it offers a targeted and potentially more effective treatment option compared to traditional methods.

Phase 1 & 2

Recruiting

Research Sponsored by ModernaTX, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Confirmed diagnosis of PA based on diagnosis by molecular genetic testing (PCCA and/or PCCB mutations)

Participant must be ≥1 year of age at the time of consent/assent if enrolled after the first 2 participants

Must not have

History of organ transplantation or planned organ transplantation during the period of study participation

Estimated glomerular filtration rate <30 milliliters (mL)/minute/1.73 square meter (m^2) as estimated by Schwartz formula for participants < 18 years of age or the Chronic Kidney Disease Epidemiology Collaboration creatinine based formula for participants ≥ 18 years of age or for participants of all ages receiving chronic dialysis

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 1 through day 22

Awards & highlights

No Placebo-Only Group

Summary

This trial tests mRNA-3927, a new treatment using messenger RNA, in people with propionic acidemia, a rare genetic disorder. The treatment helps the body make a missing protein to improve health. The study aims to find the best dose and check its safety and effectiveness.

Who is the study for?

This trial is for people aged 1 year and older with a genetic confirmation of propionic acidemia (PA). Participants must have had at least one metabolic decompensation event in the past year. They can't join if they have severe heart failure, organ transplants, certain heart rhythm issues, recent COVID-19 vaccination, or poor kidney function.

What is being tested?

The study tests mRNA-3927's safety and effectiveness in treating PA. It has two parts: first to find a safe dose that works (Dose Optimization), then to further assess this dose's efficacy and safety (Dose Expansion) by monitoring biomarkers.

What are the potential side effects?

Potential side effects are not specified but will be monitored throughout the trial as part of assessing mRNA-3927’s safety profile. This includes any adverse reactions participants might experience during the study.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have been diagnosed with PA through genetic testing.

Select...

I am at least 1 year old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have had an organ transplant or plan to have one during the study.

Select...

My kidney function is severely reduced or I am on chronic dialysis.

Select...

I have severe heart failure.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 1 through day 22

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 1 through day 22

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 1 through day 22 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Part 1: Area Under the Effect Versus Time Curve (AUEC) of 2-MC and 3-HP after Single and Repeated Administrations of mRNA-3927

Part 1: Area Under the Plasma Concentration-Time Curve (AUC) of PCCA and PCCB mRNAs

Part 1: Change From Baseline in Plasma 2-Methylcitrate (2-MC) and 3-Hydroxypropionic Acid (3-HP) Levels After Single and Repeated Administrations of mRNA-3927

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Part 1 (Dose Optimization), Part 2 (Dose Expansion), and Part 3 (Infants)Experimental Treatment1 Intervention

Part 1 (Dose Optimization): Participants (≥1 year of age) will receive single dose of mRNA-3927 by intravenous (IV) infusion every 2 weeks (Q2W) or every 3 weeks (Q3W) for up to 10 doses. Part 2 (Dose Expansion): Participants (≥1 year of age) will receive single dose of mRNA-3927 (identified during Dose Optimization Phase) by IV infusion Q2W for up to 12 months. Part 3: Participants (\<1 year of age) will receive single dose of mRNA-3927 (identified during Dose Optimization Phase) by IV infusion Q2W for up to 12 months.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Propionic Acidemia (PA) is a metabolic disorder caused by deficiencies in the enzymes propionyl-CoA carboxylase, leading to the accumulation of toxic metabolites. Traditional treatments include dietary management to limit the intake of certain amino acids and odd-chain fatty acids, and the use of medications like carnitine to help remove toxic compounds. mRNA therapy, such as the mRNA-3927 trial, aims to introduce functional mRNA into the patient's cells to produce the deficient enzymes. This approach directly addresses the root cause of PA by enabling the body to produce the necessary enzymes to metabolize propionyl-CoA properly, potentially reducing the accumulation of toxic metabolites and improving metabolic stability. This is crucial for PA patients as it offers a targeted and potentially more effective treatment option compared to traditional methods.

Fibroblast growth factor 19 as a countermeasure to muscle and locomotion dysfunctions in experimental cerebral palsy."Dietary supplementation of L-tryptophan" increases muscle development, adipose tissue catabolism and fatty acid transportation in the muscles of Hanwoo steers.Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.