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Mrna Encoding Human Glucose-6-Phosphatase Variant S298C

A new clinical trial is underway to evaluate the safety and effectiveness of mRNA-3745, a novel treatment for Glycogen Storage Disease Type 1a (GSD1a). This Phase 1/2 study aims to assess the drug’s safety, tolerability, and how it works in the body. The trial involves both single and multiple doses of mRNA-3745 given intravenously to patients with GSD1a. Researchers will closely monitor participants’ blood glucose and lactate levels, as well as other important markers related to GSD1a.

Table of Contents

What is mRNA-3745?

mRNA-3745 is an experimental medication being developed to treat a rare genetic disorder called Glycogen Storage Disease Type 1a (GSD1a)[1]. It’s a new type of treatment that uses messenger RNA (mRNA) technology, similar to some COVID-19 vaccines. The drug is also known by other names, including “mRNA encoding human G6Pase variant S298C”[1].

What condition does mRNA-3745 aim to treat?

mRNA-3745 is designed to treat Glycogen Storage Disease Type 1a (GSD1a), also known as von Gierke disease[1]. GSD1a is a rare genetic condition where the body can’t properly break down and use stored sugar (glycogen). This can lead to serious health problems, including low blood sugar (hypoglycemia), high levels of lactic acid in the blood, and liver and kidney issues[1].

How does mRNA-3745 work?

mRNA-3745 works by providing instructions to cells to produce a specific enzyme called glucose-6-phosphatase (G6Pase). In people with GSD1a, this enzyme is either missing or doesn’t work properly. The mRNA in this drug carries the code for a slightly modified version of G6Pase (called S298C) that researchers hope will work better in treating the condition[1].

The mRNA is packaged in tiny fat bubbles called lipid nanoparticles (LNPs), which help protect the mRNA and deliver it to the right cells in the body. Once inside the cells, the mRNA provides instructions to make the G6Pase enzyme, potentially helping to break down glycogen and regulate blood sugar levels[1].

Current Clinical Trial Information

mRNA-3745 is currently being studied in a Phase 1/2 clinical trial. This means it’s in the early stages of testing in humans to determine if it’s safe and if it shows promise in treating GSD1a[1].

The main goals of this study are:

  1. To evaluate the safety and tolerability of mRNA-3745 when given intravenously (through a vein) to people with GSD1a.
  2. To understand how the drug moves through and acts in the body (pharmacokinetics and pharmacodynamics).
  3. To see if the treatment can help improve blood sugar and lactate levels during fasting periods.

Who can participate in the trial?

The trial is open to people with GSD1a who meet specific criteria. Some key eligibility factors include[1]:

  • Age: Initially for adults 18 and older, with plans to include adolescents (12-17 years) and children (6-11 years) later in the study.
  • Confirmed diagnosis of GSD1a through genetic testing.
  • History of low blood sugar events.
  • Stable health condition without recent hospitalizations for low blood sugar.

There are also several factors that might prevent someone from participating, such as:

  • Previous gene therapy for GSD1a
  • History of liver transplant
  • Diagnosis of liver cancer
  • Certain other medical conditions or medications

How is the study designed?

The study is divided into two main parts[1]:

  1. Single Ascending Dose (SAD) stage: Participants receive a single dose of mRNA-3745, with different groups getting increasingly higher doses to find the right amount.
  2. Multiple Ascending Dose (MAD) stage: Participants receive multiple doses of mRNA-3745 over time.

After the initial treatment period, some participants may have the option to continue receiving the drug in an open-label extension study.

Safety Monitoring and Potential Side Effects

As with any new medication, safety is a top priority. Throughout the study, researchers will closely monitor participants for any side effects or adverse reactions. They will track things like[1]:

  • Changes in vital signs
  • Results from heart tests (ECGs)
  • Blood and urine test results
  • Any new symptoms or health issues that arise

Since this is a new treatment, all possible side effects are not yet known. Participants in the study will be informed about potential risks and will be closely monitored.

Potential Benefits of mRNA-3745

While it’s too early to know for sure if mRNA-3745 will be effective, researchers hope it might provide several benefits for people with GSD1a[1]:

  • Improved blood sugar control, potentially allowing for longer periods without eating
  • Reduced levels of lactic acid in the blood
  • Improvements in other metabolic markers associated with GSD1a
  • Potentially fewer dietary restrictions and improved quality of life

It’s important to note that as an experimental treatment, the effectiveness and long-term benefits of mRNA-3745 are still being studied. The ongoing clinical trial will help researchers better understand its potential in treating GSD1a.

Aspect Details
Drug Name mRNA-3745
Target Condition Glycogen Storage Disease Type 1a (GSD1a)
Study Type Phase 1/2, adaptive, open-label, single ascending dose to multiple ascending dose
Main Objective Evaluate safety and tolerability of mRNA-3745
Secondary Objectives Assess pharmacodynamics, pharmacokinetics, and effects on GSD1a metabolic biomarkers
Participant Age Groups Adults (≥18 years), Adolescents (12-17 years), Children (6-11 years)
Administration Method Intravenous (IV) injection
Study Design Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) stages
Key Assessments Blood glucose and lactate levels during fasting challenges, safety monitoring, pharmacokinetic parameters
Follow-up Period Up to 52 weeks after study drug administration

FAQ

  • What is mRNA-3745? mRNA-3745 is a new drug being tested for the treatment of Glycogen Storage Disease Type 1a (GSD1a). It contains mRNA that encodes for a variant of the human glucose-6-phosphatase enzyme, which is deficient in people with GSD1a.
  • How is mRNA-3745 administered? mRNA-3745 is given through intravenous (IV) injection, which means it's delivered directly into the bloodstream.
  • What are the main goals of this clinical trial? The main goals are to evaluate the safety and tolerability of mRNA-3745 in patients with GSD1a, and to understand how the drug works in the body (its pharmacokinetics and pharmacodynamics).
  • Who can participate in this clinical trial? The trial includes adults (18 years and older), adolescents (12-17 years), and children (6-11 years) with a confirmed diagnosis of GSD1a. Participants must meet specific health criteria and be willing to comply with the study procedures.
  • What will participants experience during the trial? Participants will receive either single or multiple doses of mRNA-3745. They will undergo various tests and assessments, including blood tests, fasting challenges, and monitoring of glucose and lactate levels. The study includes different stages and follow-up periods to assess both short-term and long-term effects of the treatment.

Ongoing Clinical Trials on Mrna Encoding Human Glucose-6-Phosphatase Variant S298C

  • Study on the Safety and Effects of mRNA-3745 for Patients with Glycogen Storage Disease Type 1a (GSD1a)

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France The Netherlands Poland Spain

Glossary

  • Glycogen Storage Disease Type 1a (GSD1a): A rare genetic disorder where the body cannot break down stored glucose properly, leading to low blood sugar levels and other metabolic problems.
  • mRNA: Messenger RNA, a type of genetic material that carries instructions for making proteins in the body.
  • Glucose-6-phosphatase: An enzyme that helps release glucose from its stored form in the liver. This enzyme is deficient in people with GSD1a.
  • Intravenous (IV): A method of administering medication directly into a vein.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including how it's absorbed, distributed, metabolized, and eliminated.
  • Pharmacodynamics (PD): The study of how a drug affects the body, including its mechanism of action and the body's response to the drug.
  • Single Ascending Dose (SAD): A part of the study where participants receive a single dose of the drug, with doses increasing for each new group of participants.
  • Multiple Ascending Dose (MAD): A part of the study where participants receive multiple doses of the drug over time, with doses increasing for each new group of participants.
  • Fasting challenge: A test where participants go without food for a set period to assess how their body manages blood sugar levels.
  • Biomarkers: Measurable indicators in the body that can show the effects of a disease or treatment, such as blood glucose or lactate levels in this study.

References

  1. http://clinicaltrials.eu/trial/study-on-the-safety-and-effects-of-mrna-3745-for-patients-with-glycogen-storage-disease-type-1a-gsd1a/