Gene Therapy for Cerebral Adrenoluekodystrophy (CALD) in Boys 

Heena Cho | October 13, 2022

At $3 million, Skysona is now the world’s most expensive drug. American biotechnology company bluebird bio recently won accelerated FDA approval for Skysona, a gene therapy treatment that aims to treat boys from ages 4 to 17 suffering from early cerebral adrenoleukodystrophy (CALD). CALD is a rare and fatal neurological disorder caused by mutations in the ABCD1 gene that results in the build up of long fatty acids in the nervous system and blood. CALD mostly affects young boys and progresses rapidly after the first symptoms appear, leading to a complete loss of voluntary movement. 

What is Gene Therapy?

Skysona is not the only multimillion dollar drug. Other gene therapy treatments such as Zolgensma and Zynteglo cost more than $2 million per dose. This astonishing price tag is reflected in the nature of gene therapy – treating diseases by manipulating or modifying the expression of genes. The human genetic code contains the blueprint that drives protein synthesis, which is the basis of all our biological processes. When these genes are affected by mutations, diseases could potentially occur. Around 300 million people worldwide live with genetic diseases, but common treatment options such as chemotherapy and surgery are not always effective when it comes to preventing or treating such conditions. Because gene therapy targets the underlying cause of a genetic disease – the defective gene – it has the potential to dramatically improve the patient’s condition.

According to the FDA, gene therapy can occur through several mechanisms: 

1. Replacing the disease causing-gene with a healthy copy 
2. Inactivating a disease-causing gene that is not functioning properly
3. Introducing a new or modified gene into the body to help treat a disease

Gene Therapy and Cancer Treatment                                                      

Ever since the first human trial in 1990, scientists have been looking for a way to utilize gene therapy to treat a wide variety of diseases ranging from cancer to hemophilia. In 2016, chimeric antigen receptor (CAR) T cell therapy was especially effective against lymphoblastic leukemia, a common childhood cancer. The therapy involved removing the patient’s own immune cells (T cells) and genetically altering them so they could recognize and target cancer cells. Afterwards, the genetically altered T cells were put back into the patient through the bloodstream. Researchers at the University of Pennsylvania discovered that a single modified T cell could kill as many as 100,000 lymphoblasts while reproducing and retaining their ability. 

Vanderbilt also offers CAR T cell therapy; in 2017, Vanderbilt-Ingram Cancer Center was selected as one of the few centers in the United States to provide FDA-approved CAR T cell therapy for adults with a specific type of lymphoma. 

Gene therapy’s advantage as a single infusion treatment is reflected in CAR T cell therapy. The entire procedure takes a few weeks, and patients usually experience rapid recovery. Compare this to aggressive chemotherapy, a grueling process that typically lasts 3 to 6 months, and it is easy to see why gene therapy is attracting so much attention. CAR T cell therapy is also effective with achieving remissions. Because the altered T cells stay in the body for a long time, they can attack cancer cells even when the patient experiences a relapse. Studies have shown that 9 out of 10 acute lymphoblastic leukemia patients who did not experience success with other treatments had full remission with CAR T cell therapy. 

Risks in Gene Therapy

As amazing and effective as it can be, gene therapy has its risks and technical difficulties. One of CAR T cell therapy’s most common side effects is cytokine release syndrome (CRS). The complication occurs when CAR T cells release cytokines, causing an immune system reaction accompanied by fevers, fatigue, nausea, difficulty breathing, dizziness, and more.

Moreover, since genes can’t be simply inserted into human cells, a carrier called a vector is needed. Viruses serve as common vectors because they can recognize cells and carry genetic material; however, they also present the possibility of infection and tumor formation. Researchers are working on better ways to deliver genetic material without viruses. 

Bumps lie ahead in gene therapy research and implementation, but it is sure to redefine human diseases treatment and the way we use drugs. 

Works Cited:

Abramson Cancer Center. (n.d.). CAR T Cell Therapy. Pennmedicine.org. Retrieved October 9, 2022, from https://www.pennmedicine.org/cancer/navigating-cancer-care/treatment-types/immunotherapy/what-is-car-t-therapy 

Beer, T. C. (2022, June 14). CAR T-Cell Therapy: Frequently Asked Questions. Lancastergeneralhealth.org. Retrieved October 9, 2022, from https://www.lancastergeneralhealth.org/health-hub-home/2022/june/car-t-cell-therapy-frequently-asked-questions 

Daley, J. (2021, November 1). Four success stories in Gene therapy – scientific american. Scientific American. Retrieved October 9, 2022, from https://www.scientificamerican.com/article/four-success-stories-in-gene-therapy/ 

FDA. (n.d.). What is gene therapy? U.S. Food and Drug Administration. Retrieved October 9, 2022, from https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy

Liu, A. (2022, September 19). A $3M gene therapy: Bluebird bio breaks its own pricing record with FDA approval of Skysona. Fierce Pharma. Retrieved October 9, 2022, from https://www.fiercepharma.com/pharma/3m-gene-therapy-bluebird-breaks-own-record-fda-approval-skysona 

Malcolm, E. (2019, January 23). Childhood Cerebral Adrenoleukodystrophy (CALD) . Adrenoleukodystrophy News. Retrieved October 9, 2022, from https://adrenoleukodystrophynews.com/childhood-cerebral-adrenoleukodystrophy-cald/ 

Rutgers Cancer Institute of New Jersey. (n.d.). Advantages of CAR-T cell therapy. Advantages of CAR-T Cell Therapy | Rutgers Cancer Institute of New Jersey. Retrieved October 9, 2022, from https://www.cinj.org/patient-care/advantages-car-t-cell-therapy 

Vanderbilt University Medical Center. (2017, October 25). Vanderbilt-Ingram Cancer Center patients treated with new FDA-approved CAR T therapy. Retrieved October 9, 2022, from https://news.vanderbilt.edu/tag/car-t-therapy/ 

Images:

3.20 Gene Therapy. CK-12 Foundation. (2021, May 24). Retrieved October 9, 2022, from https://flexbooks.ck12.org/cbook/ck-12-middle-school-life-science-2.0/section/3.20/primary/lesson/gene-therapy-ms-ls/ 

Collins, F. S. (2019). A new gene is injected into an adenovirus vector, which is used to introduce the modified DNA into a human cell. National Institutes of Health. Retrieved October 9, 2022, from https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-streamlines-gene-therapy-oversight-charts-course-considering-emerging-technology.