Gene Therapy Program -

Why Gene Therapy for Friedreich’s Ataxia (FA)?

Currently, there is no cure for FA. However, gene therapy offers a revolutionary approach by delivering a functional copy of the FXN gene directly into affected cells, potentially stopping or even reversing the disease’s progression.

Gene therapy has already transformed the treatment of several rare diseases. FA is a strong candidate for this breakthrough.

Detailed Steps in a Gene Therapy Program

*The arrow indicates where we are in the program

Research and Design

In this first step, researchers focus on understanding the genetic cause of the disease and developing a therapy that can correct or replace the faulty genes.

Researchers create a genetic design, selecting a method for delivering the therapeutic gene (e.g., viral vectors such as AAV – Adeno-associated virus).
The specific genes that need to be targeted to halt the progression of the disease are identified.

Preclinical Research and Testing

Before testing in humans, the gene therapy must be validated through animal models. This step studies how the therapy works in the body and whether any side effects or issues may arise.

Plasmid Design: To create viral vectors, plasmids – small pieces of DNA that allow the insertion of the therapeutic gene into the virus – are used.

Plasmid design is crucial to ensure the virus can deliver the correct gene to the right cells.

What is Plasmid preparation?

This is the first step in manufacturing gene therapy. Plasmids, which are circular DNA molecules, are designed and produced. These plasmids contain:

The therapeutic gene (e.g., a healthy copy of FXN for Friedreich’s ataxia).
Necessary regulatory sequences to control gene expression.

Plasmids are produced in bacteria, as they can replicate plasmids in large quantities. Once the plasmids are ready, they are used in the next step – viral preparation.

What is Viral preparation?

This step involves using the plasmids to produce viral vectors, such as AAV9. It takes place in human cells (often HEK293 cells), which act as biological factories to produce virus particles.

The process follows these steps:

Transfection – Introducing plasmids into HEK293 cells, which then start producing AAV9 viruses containing the therapeutic gene.
Virus Production – The cells manufacture and release AAV9 viruses into the culture medium.
Virus Purification – The AAV9 particles are separated and concentrated from other cell material.
Quality Control – The virus’s purity, concentration, and functionality are analyzed.

Animal Model Testing: Animals carrying a model of Friedreich’s ataxia are used to evaluate whether the therapy produces the desired effect

Proof of Concept (POC)

This is the critical test phase: Proof of Concept. Here, we begin the first phase of clinical trials to test the therapy on humans and prove that it works in the human body.

This phase focuses on proving safety and whether the therapy produces the expected results. It is the first step in determining if our genetic material can successfully deliver the correct gene to the target cells and function properly.
At this stage, we also assess whether the virus (carrying the therapeutic gene) can deliver the correct gene to the right location without causing harm or unwanted side effects.

Clinical Trials (Phases 1–3)

If the POC tests are positive, we proceed to larger and more extensive clinical trials. These studies determine whether the therapy works in larger groups of people and ensure its safety and long-term efficacy.

Phase 1 (Safety Testing): The therapy is tested on a small group of people to ensure there are no severe side effects.
Phase 2 (Efficacy Testing): The therapy is administered to a larger group of patients to understand its effectiveness and whether the dosage needs adjustment.
Phase 3 (Large-Scale Testing): The therapy is tested on an even larger number of patients to obtain a clear understanding of its effectiveness and safety in a broader population.

Regulatory Approval

If the results from clinical studies are positive, we seek approval from regulatory agencies such as the FDA (in the USA) or EMA (in the EU). This process involves authorities reviewing all study data and deciding whether the therapy can be approved for public use.

Once approved, the treatment can be distributed to clinics and hospitals where patients can start receiving therapy.

Market and Distribution

After receiving approval, the therapy is distributed to clinics and hospitals where patients can receive treatment. However, the work doesn’t stop there:
Ongoing research and follow-up studies ensure that the treatment remains effective long-term and is improved if necessary.
Research continues to apply the same therapy to other diseases and expand the technology’s applications.

Proof of Concept (POC) is the most critical step in the gene therapy program. This is where we determine whether the therapy truly works in humans. If it succeeds, it could be a breakthrough that changes the way we treat entire disease groups. If it fails, we may need to adjust or develop a new strategy. This step is crucial for the entire program’s future.

Why Parents Like Us Can Move Faster Than Any Company

Developing gene therapies within traditional pharmaceutical companies is often a lengthy and expensive process, typically taking between 10 and 15 years from research to a finished treatment, with costs reaching several hundred million USD.

As parents and researchers, we have a personal drive to find effective solutions swiftly. Our decision-making process is direct and focused, eliminating bureaucratic obstacles and enabling faster progress. Through close collaboration with leading experts and patient groups, we can accelerate development and reduce costs.

Our drive is personal. Our goal is clear. And we don’t have time to wait.