Gene Therapy: How DNA Code Reprogramming Helps Treat Rare Diseases

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Gene therapy is a treatment method based on modifying genetic material in cells by replacing, deleting, or adding missing genes. Currently, more than 7,000 diseases are known, each accompanied by multiple mutations in a specific gene or chromosomal abnormalities. The goal of treating rare diseases is to address the root cause rather than merely alleviate symptoms. As a result, gene therapy contributes to long-term improvements in patients’ quality of life and the restoration of body functions.

According to the WHO, orphan (rare) diseases occur in 1 in 2,000 cases or even less frequently. Despite their low prevalence, the problem is global. Diagnosis of such diseases is difficult and represents a real quest for patients. The search for the correct diagnosis can take years, involving visits to multiple doctors. First, physicians may not be familiar with all diseases and may never encounter them in practice. Second, the symptoms are often ambiguous and non-specific, resembling those of more common illnesses. Third, confirmation requires advanced genetic testing, which is not available in every clinical laboratory.

When it comes to treatment, there are also some pitfalls. Even when a complex diagnosis is made, it is not always possible to find the necessary drug. Pharmaceutical companies are not interested in producing drugs for rare diseases, explaining that clinical trials require huge financial investments, and the sales market is extremely small. And the pharmaceutical product itself is extremely expensive.

The European Organisation for Rare Diseases (EURORDIS) estimates that about 30 million people in Europe are affected by rare pathologies, which is about 6-8% of the population. In the USA, this number has also reached 25-30 million people (10% of the population), as indicated by statistics from the National Institutes of Health (NIH).

Common Categories of Orphan Diseases

80% of rare diseases have a genetic origin. The following groups are distinguished:

• Neurological disorders affect the brain, spinal cord, and peripheral nerves, primarily causing motor dysfunction. In 65% of cases, rare neurological diseases lead to severe disability. Examples include hereditary spastic paraplegia (Strümpell disease), spinal muscular atrophy types 1 (Werdnig-Hoffmann) and 2, amyotrophic lateral sclerosis, West syndrome, Dravet syndrome (epilepsy), and congenital muscular dystrophy.
• Oncological diseases include about 50 types of rare malignant tumors, such as lip cancer, Merkel cell carcinoma (skin cancer), Sézary syndrome (lymphoma), and thymoma (thymus cancer).
• Blood disorders include various types of anemia (low hemoglobin levels), such as paroxysmal nocturnal hemoglobinuria, sickle cell anemia, Diamond-Blackfan anemia, and Fanconi anemia. This category also includes von Willebrand disease, which causes spontaneous episodic bleeding.
• Autoimmune diseases result from immune system dysregulation. Examples include Evans syndrome and Sjögren’s syndrome.

Traditional Treatments for Rare Diseases

Traditional therapies for orphan diseases include:

• Symptomatic therapy aimed at alleviating symptoms (pain, inflammation). Disadvantages: The disease continues to progress, leading to new, more severe symptoms.
• Replacement therapy involves introducing the missing enzyme or hormone (e.g., in Gaucher disease). Disadvantages: Requires continuous treatment and has side effects.
• Immunosuppressive therapy suppresses the immune system in autoimmune diseases. Disadvantages: by suppressing the immune system, the risk of infectious diseases increases. Also, immunosuppressants are potentially toxic to the liver and kidneys.
• Chemotherapy and radiotherapy are used for cancer treatment. Disadvantages: Many side effects and harmful impact on healthy cells.

How Does Gene Therapy Work?

Gene therapy represents a revolutionary breakthrough in medicine, offering patients with incurable diseases a chance at recovery. Its primary goal is to target defective genes to correct or compensate for them. The principles of gene therapy rely on three mechanisms: restoring gene function, adding a missing gene, or suppressing the activity of a “faulty” gene. The most common therapy is gene insertion therapy, where the gene is produced by polymerase chain reaction from another person’s normal deoxyribonucleic acid.

Technologies for Introducing Normal DNA into Cells

Viral Transfection

Viruses, due to their small size, have the natural ability to enter cells and leave their genetic material there. This has led scientists to modify viruses, giving them useful information that cannot harm the host cell. This approach is actively developed in Israel and the U.S.

Liposomes

Small fat-containing vesicles serve as vectors for genetic material. DNA and RNA are encapsulated in liposomes and inserted into the body. Liposomal vectors are considered safer than viral vectors because they do not trigger the immune system. This technology is widely used in Europe and China.

Chemical Modification

Chemicals are used to increase or decrease the activity of specific genes. They change the function of genes and therefore the production of certain proteins. The method is effective in treating rare types of cancer.

Antisense Nucleic Acids

In this method, normal genes are not introduced into the body, instead, pathological genes are switched off. The development of drugs based on this method is carried out by the American company NS Pharma and the Japanese company Nippon Shinyaku. Despite the fact that this technique is still at the stage of experimental development, it is already being used in the world’s top clinics to treat spinal muscular atrophy and Duchenne myodystrophy. In addition, USA scientists have created a form of small molecules of antisense nucleotides that can pass through the blood-brain barrier. In the near future, this type of gene therapy will be used to treat amyotrophic lateral sclerosis.

CRISPR-Cas9

CRISPR-Cas9 is a powerful modern gene editing technology used in gene therapy. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is part of the immune system of bacteria that protects them from viruses. Bacteria memorise fragments of viral DNA and use them to identify and destroy viruses. Cas9 is a “scissor” protein that cuts DNA at specific sites. The advantages of CRISPR-Cas9 include the accuracy of DNA chain changes, speed, efficiency and relative financial availability. Leading foreign clinics use the latest editing technology to treat cystic fibrosis and sickle cell anaemia.

Examples of Successful Gene Therapy Developments

The world’s major research centers are actively engaged in the development of gene therapy and implementation of thoroughly tested innovations in medicine.

Luxturna (voretigene neparvovec): The first approved genetic therapy for inherited retinal dystrophy (IRD) caused by RPE65 mutations. Introduced in 2017, it restores vision and prevents severe complications, including blindness.

Zolgensma (onasemnogene abeparvovec): Approved in 2019 for treating spinal muscular atrophy (SMA). It delivers an adenoviral vector carrying the SMN1 gene into motor neurons. A single injection of the drug is sufficient to treat SMA. The earlier the therapy is started, the more favorable the outcome will be.

Kymriah (tisagenlecleucel): CAR-T therapy for rare cancers like acute lymphoblastic leukemia (ALL) and Diffuse large B-cell lymphoma. It modifies the patient’s T cells to target and destroy malignant cells.

Strimvelis: developed for the treatment of severe combined immunodeficiency (ADA-SCID) in children with adenosine deaminase deficiency caused by a mutation in the ADA gene. Stem cell gene therapy is approved by the European Commission and is highly effective in compensating for disorders of humoral and cellular immunity.

Viltepso: is a new drug, which is an antisense oligonucleotide for the treatment of Duchenne muscular dystrophy in patients with a confirmed dystrophin gene mutation (DMD). Has demonstrated a high level of efficacy and safety during clinical trials. To date, it has been approved by the U.S. Food and Drug Administration (FDA) and registered in 4 countries.

Diseases Treatable with Gene Therapy

The successful application of gene therapy emphasizes its potential to treat rare and severe forms of diseases. Let us summarize the results and tell you which pathologies are amenable to innovative gene technologies.

• Cystic fibrosis: Corrects mutations in the CFTR gene.
• Hemophilia: Introduces a functional gene to produce clotting factor.
• Spinal muscular atrophy: Restores SMN1 gene function for motor neuron survival.
• Hereditary retinal degeneration: Delivers corrected genes to retinal cells to restore vision.
• Sickle cell anemia: LentiGlobin viral vector therapy corrects HBB gene mutations.
• Acute lymphoblastic leukemia and non-Hodgkin’s lymphoma: CAR-T cell therapy modifies immune cells.
• Age-related macular degeneration: Gene therapy introduces protective genes to slow disease progression or restore retinal function.

Challenges in Choosing an Overseas Clinic for Treatment

The first major challenge is the overwhelming amount of information, making it difficult for patients to navigate the medical field. Hundreds of clinics worldwide offer gene therapy, but not all of them have a solid reputation. Some medical institutions promise rapid results but, in reality, lack sufficient experience in performing high-precision therapy.

The second challenge is financial. Gene therapy is an expensive treatment for rare diseases. Some clinics offer special payment conditions, but this information is often not readily available to patients.

The third difficulty in planning treatment is the availability of medications. Not every new development is accessible in clinics that offer gene therapy, and not all drugs may be approved in a particular country.

In such cases, turning to professionals is a well-considered and rational decision. Hospitality Medservice has extensive experience in medical tourism, allowing us to select the most suitable hospitals for patients based on their specific needs. We know where to undergo cutting-edge gene therapy that meets all international standards and can find the right clinic in the shortest possible time. Additionally, we provide insights into all the details and special conditions offered by leading global clinics.

Hospitality Medservice — your reliable partner in finding the best clinic worldwide. Our website features only reputable medical institutions with top-notch equipment and the latest treatment protocols. Evaluate the clinic’s level, get acquainted with the doctors, compare treatment costs, and reach out to us for assistance in organizing:

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The text has been verified

Verified by: Marianna Sharipova, Certified Physician, Medical Director of HMS, with 20 years of experience in medical tourism.

Author: Anna Kukarkina, MD