a new era in genetic disorder treatment

a new era in genetic disorder treatment

In a significant leap forward for medical science, recent breakthroughs in gene therapy are ushering in a new era of treatment for various human diseases. The field of gene therapy, which involves manipulating or introducing genetic material into a person’s cells to treat or prevent disease, has seen remarkable advancements, with several gene therapy drugs receiving approval from the Food and Drug Administration (FDA).

Gene therapy has emerged as a groundbreaking frontier in the treatment of genetic disorders, offering hope and transformative possibilities for individuals grappling with conditions such as sickle cell disease, thalassemia, and hemophilia. In 2024, the landscape of health care is witnessing remarkable advancements with FDA-approved gene therapy treatments that hold the potential to revolutionize the lives of patients around the world.

Broadly offered through two means, commercial gene therapy approaches look to augment or edit the genome to enhance human capacity by “balancing” or “fixing” the underlying genetic defect, usually in monogenetic disorders. The “ex-vivo” gene therapy approaches attempt to “edit” the human genome by using mechanisms like CRISPR Cas-9, zinc finger nuclease, Cas-12, etc., in order to “augment” the genome at precise locations to affect downstream protein synthesis, thereby altering the course of the disease positively for the patient. The “In-vivo” gene therapy focuses on “gene-addition” by supplementing a missing sequence of nucleotide/protein, encapsulated in a vector which is then delivered as an intravenous infusion, thereby altering protein synthesis to positively impact outcomes in the patient.

Some examples of these mechanisms in action are explained below:

Sickle cell disease (SCD). A hereditary blood disorder characterized by abnormally shaped red blood cells has long posed significant challenges for both patients and health care providers. However, recent FDA approval of the gene therapy drugs exagamglogene autotemcel and lovotibeglogene autotemcel marks a turning point in the management of this condition. Exagamglogene autotemcel works by introducing a modified gene into the patient’s hematopoietic stem cells using CRISPR-based gene editing tools, while lovotibeglogene autotemcel uses a lentiviral vector to do the same, promoting the production of healthy red blood cells and mitigating the impact of sickle-shaped cells. Clinical trials have shown promising results, likely leading to FDA approval for both agents in the USA.

Thalassemia. Thalassemia, a group of blood disorders affecting hemoglobin production, has also seen notable advancements in gene therapy. The FDA approval of betibeglogene autotemcel represents a breakthrough for individuals with thalassemia major. Betibeglogene autotemcel employs an approach, introducing a corrected gene into the patient’s bone marrow cells. This innovative therapy aims to restore normal hemoglobin production, reducing the need for frequent blood transfusions and alleviating the burden on patients.

Hemophilia. Hemophilia B, a rare bleeding disorder caused by a deficiency of clotting factors, has traditionally required lifelong management through clotting factor replacement therapies. However, the FDA’s approval of etranacogene dezaparvovec heralds a new era for hemophilia treatment. Etranacogene dezaparvovec employs gene therapy to enhance the production of clotting factors within the patient’s liver cells. This approach aims to provide a sustained and natural source of clotting factors, reducing the reliance on frequent infusions and promises to deliver a better quality of life with infrequent bleeding. The price tag, a whopping $3.5 million per dose, may be out of reach for most patients with this disorder in Asia, though.

Global accessibility. One of the significant advantages of these FDA-approved gene therapy treatments is their potential for global accessibility. Pharmaceutical companies and health care organizations are actively working to ensure that these groundbreaking therapies reach patients in diverse regions, transcending geographical boundaries. Collaborative efforts are underway to make these treatments available in countries where these genetic disorders are prevalent, thereby extending the benefits of gene therapy to a broader population.

Challenges and considerations. While the strides in gene therapy are undeniably promising, challenges persist, including the need for rigorous long-term safety monitoring, addressing potential side effects, and ensuring equitable access to these innovative treatments. Additionally, the evolving landscape of gene therapy research underscores the importance of ongoing scientific inquiry and ethical considerations to optimize patient outcomes. The monumental costs associated with these approved therapies are out of reach for most patients in sub-Saharan Africa and India, where the bulk of the suffering patients reside.

These transformative therapies signify a shift towards personalized, targeted approaches to genetic disorders, offering not just treatment but the potential for a substantially improved quality of life for those who have long battled these challenging conditions. As the global health care community continues to embrace these advancements, the future holds promise for further breakthroughs and increased accessibility to gene therapy treatments for patients around the world. With global integration of health care and adaptation of skills through academic east-west partnerships, many such groundbreaking therapies should see themselves reach the global south.

Akshat Jain is a pediatric hematology-oncology physician.


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