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Fragment Antibody Targeting Human Tfr1 Conjugated To Phosphorodiamidate Morpholino Oligomer

A groundbreaking clinical trial is underway to assess the safety, efficacy, and potential benefits of DYNE-251, a new drug designed to treat Duchenne Muscular Dystrophy (DMD). This study focuses on patients with DMD who are suitable for exon 51 skipping, a specific genetic mutation. The trial aims to evaluate how well DYNE-251, administered intravenously, can improve muscle function and increase dystrophin protein levels in patients with this debilitating condition.

Table of Contents

What is DYNE-251?

DYNE-251 is a new medication being developed to treat Duchenne muscular dystrophy (DMD)[1]. It is classified as a biological/biotechnological product, which means it is made using living organisms or their products. The active substance in DYNE-251 is called a fragment antibody targeting human TFR1 conjugated to phosphorodiamidate morpholino oligomer. This long name describes the two main parts of the medication:

  1. A fragment of an antibody that targets a specific protein in the body called TFR1
  2. A special molecule called a phosphorodiamidate morpholino oligomer (PMO) that is attached to the antibody fragment
DYNE-251 is also known by other names, including “Fab targeting human TfR1 conjugated to a PMO”[1].

How Does DYNE-251 Work?

DYNE-251 is designed to work through a process called exon 51 skipping[1]. In patients with DMD, there is a problem with the gene that makes a protein called dystrophin. This protein is crucial for maintaining muscle strength. The exon 51 skipping approach aims to “skip over” the problematic part of the gene, allowing the body to produce a shorter but partially functional version of the dystrophin protein.

The medication is given through intravenous infusion, which means it’s delivered directly into the bloodstream through a vein[1]. This method helps ensure that the medication can reach muscles throughout the body.

Target Condition: Duchenne Muscular Dystrophy

DYNE-251 is being developed to treat Duchenne muscular dystrophy (DMD)[1]. DMD is a genetic disorder characterized by progressive muscle degeneration and weakness. It primarily affects boys and is caused by mutations in the dystrophin gene. This gene is responsible for producing the dystrophin protein, which is essential for maintaining the structure and function of muscle fibers.

Clinical Trial Details

DYNE-251 is currently being studied in a Phase 1/2 clinical trial[1]. This means it’s in the early stages of testing in humans. The study is designed as a randomized, double-blind, placebo-controlled trial, which helps ensure that the results are as unbiased and accurate as possible. Here are some key details about the trial:

  • It’s a multiple ascending dose study, which means different groups of participants will receive increasing doses of the medication to determine the safest and most effective dose.
  • The study will assess the safety, tolerability, pharmacodynamics, efficacy, and pharmacokinetics of DYNE-251. These terms refer to how safe the drug is, how well it’s tolerated, what effects it has on the body, how effective it is, and how it’s processed by the body.
  • Participants will receive multiple intravenous doses of DYNE-251 over the course of the study.

Eligibility Criteria

The study has specific criteria for who can participate[1]. Some key inclusion criteria are:

  • Boys aged 4 to 16 years
  • Confirmed diagnosis of DMD with a mutation that could benefit from exon 51 skipping
  • Ability to undergo a muscle biopsy
  • Stable dosage of glucocorticoids for at least 12 weeks before starting the study
  • Adequate heart function
There are also exclusion criteria, such as:
  • Uncontrolled symptoms of heart failure
  • Recent major surgery or planned surgery during the study
  • Need for daytime ventilator assistance
  • Recent use of other experimental treatments for DMD

Study Objectives

The main objectives of the study are[1]:

  1. To evaluate the safety and tolerability of DYNE-251
  2. To measure dystrophin protein levels in muscle tissue after treatment
  3. To assess the effectiveness of exon skipping
  4. To evaluate muscle function
  5. To study how the drug is processed by the body
  6. To check for any immune responses to the medication

Potential Benefits

While it’s important to note that the effectiveness of DYNE-251 is still being studied, the potential benefits being investigated include[1]:

  • Increased production of dystrophin protein in muscle tissue
  • Improved muscle function
  • Reduced muscle damage (as measured by blood creatine kinase levels)
These potential benefits could lead to improved quality of life for patients with DMD, but more research is needed to confirm these effects.

Safety Considerations

As with any new medication, safety is a top priority in the DYNE-251 clinical trial[1]. The study will closely monitor for any side effects or adverse events. Participants will be regularly assessed for:

  • Any new symptoms or health issues that arise during the study
  • Changes in heart and lung function
  • Immune reactions to the medication
It’s important to remember that as DYNE-251 is still in the early stages of testing, not all potential risks may be known at this time.

Aspect Details
Drug Name DYNE-251 (Fragment Antibody Targeting Human TfR1 Conjugated to Phosphorodiamidate Morpholino Oligomer)
Condition Duchenne Muscular Dystrophy (DMD) amenable to exon 51 skipping
Trial Phase Phase 1/2
Administration Intravenous infusion
Primary Objectives Evaluate safety, tolerability, and changes in dystrophin protein levels
Secondary Objectives Assess exon skipping, muscle function, pharmacokinetics, and immunogenicity
Key Eligibility Males aged 4-16 years with confirmed DMD diagnosis amenable to exon 51 skipping
Study Duration Up to 145 weeks (approximately 3 years)

FAQ

  • What is DYNE-251 and how does it work? DYNE-251 is a fragment antibody targeting human TfR1 conjugated to a phosphorodiamidate morpholino oligomer (PMO). It is designed to skip exon 51 in the dystrophin gene, potentially allowing for the production of a shortened but functional dystrophin protein in patients with Duchenne Muscular Dystrophy.
  • Who is eligible for this clinical trial? The trial is open to male patients aged 4 to 16 years with a confirmed diagnosis of DMD and a mutation in the dystrophin gene that is amenable to exon 51 skipping. Participants must have been on a stable dose of glucocorticoids for at least 12 weeks prior to the start of the study.
  • How is DYNE-251 administered in the trial? DYNE-251 is administered intravenously (IV) in multiple doses throughout the study. The exact dosing schedule may vary between different cohorts in the trial.
  • What are the main objectives of this clinical trial? The main objectives are to evaluate the safety and tolerability of DYNE-251, assess changes in dystrophin protein levels in muscle tissue, measure exon skipping effectiveness, and evaluate improvements in muscle function in patients with DMD.
  • How long does the clinical trial last? The trial includes assessments up to Week 145, which is nearly 3 years. This extended period allows researchers to evaluate the long-term effects and safety of DYNE-251 in patients with DMD.

Ongoing Clinical Trials on Fragment Antibody Targeting Human Tfr1 Conjugated To Phosphorodiamidate Morpholino Oligomer

  • Study of DYNE-251 safety and effectiveness in patients with Duchenne muscular dystrophy who are candidates for exon 51 skipping treatment

    Not recruiting

    2 1
    Investigated diseases:
    Investigated drugs:
    Belgium Ireland Italy Spain

Glossary

  • Duchenne Muscular Dystrophy (DMD): A genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin that helps keep muscle cells intact.
  • Exon 51 Skipping: A therapeutic approach for DMD that aims to skip over a faulty section of genetic code (exon 51) to allow the production of a shortened but partially functional dystrophin protein.
  • Dystrophin: A protein that helps keep muscle cells intact. In DMD, this protein is absent or non-functional, leading to muscle weakness and degeneration.
  • Phosphorodiamidate Morpholino Oligomer (PMO): A synthetic molecule used in exon skipping therapy to modify gene expression and potentially restore dystrophin production in DMD patients.
  • Creatine Kinase (CK): An enzyme found in various tissues, especially muscles. Elevated levels in the blood can indicate muscle damage or disease.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion.
  • Immunogenicity: The ability of a substance to provoke an immune response in the body.
  • Anti-Drug Antibodies (ADAs): Antibodies produced by the immune system in response to a therapeutic drug, which may affect the drug's efficacy or safety.
  • Percent Predicted Forced Vital Capacity (FVC): A measure of lung function that compares a person's forced vital capacity to the average FVC of people of similar age, height, and sex.
  • Performance of Upper Limb (PUL) Scale: A standardized test used to measure upper limb function in patients with DMD.

References

  1. http://clinicaltrials.eu/trial/study-of-dyne-251-for-patients-with-duchenne-muscular-dystrophy-suitable-for-exon-51-skipping/