Genetic Innovations in Epilepsy Treatment: Decoding the Duo of Gene Addition and Gene Editing

By:  Marae R. Laws

Photo Credit: www.depositphotos.com

Introduction

Gene therapy is the process of modifying a person’s genes to treat or cure a genetic disorder. Gene therapy serves as a valid treatment option for genetic epilepsy patients. Methods such as gene addition and gene editing can help reduce and even eliminate the abnormality of a seizure-prone gene. Genetic epilepsies occur when an inherited gene, or several genes, have the likelihood of being prone to seizures. Although epilepsies such as nocturnal frontal epilepsy result from a genetic defect, commonly hereditary, the cause does not have to be inherited by the parents. Defective genes can be present in an individual despite their absence in either parent.

History of Gene Therapy

In the 1960s, scientists sought to cure genetic disorders such as monogenic diseases and hereditary diseases like hemophilia, cystic fibrosis, and nocturnal frontal epilepsy by inserting DNA sequences into the cells of patients. This insertion would result in a properly functional gene and a better alternative to taking drugs or surgery. The overall goal was to improve conditions if finding a cure could not be done. There were initially three tested methods within gene therapy before being utilized on an actual patient; the first method included injecting DNA sequences with a micropipette directly into the living mammalian cell. The second was cell exposure to a strand of DNA containing the desired genes. The third required a virus as a form of transportation from the normal gene to the abnormal cell. Today, gene therapy utilizes various techniques and methods, such as gene delivery, which is the process of taking foreign genetic material and directing it to a host cell; gene transfers, also known as gene addition, which introduces new DNA into existing cells by vectors like viruses; and gene editing, which is a new technique that essentially changes existent DNA in the cell. French Anderson is known as the father of gene therapy due to successfully utilizing the gene addition method to cure a four-year-old girl with a hereditary genetic disease called adenosine deaminase deficiency. During the procedure, normal ADA genes entered the patient’s T-lymphocytes. The added genes grew in culture as white cells returned to her system. Anderson’s work was dubbed the first successful gene transfer in 1990.

Gene Addition in Epilepsy

Gene Edition is the process of taking a normalized DNA sequence and inserting it into an abnormal or missing cell through a vector to which these vectors are either viral or non-byrally engineered. Before an epilepsy patient undergoes gene addition, the patient must undergo a gene test, an analysis of the patient’s chromosomes and whether or not they are balanced. In the unfortunate case that their chromosomes are imbalanced, meaning they are either missing or have too many pieces of chromosomes, the doctor analyzing these chromosomes can decide the correct medical treatment for a patient. When a patient is missing parts of their chromosome or missing an entire chromosome, gene addition comes into perfect play as it takes new DNA sequences or pieces of genetic material and uses this as a vector to transport that material into the abnormal or missing chromosome, bringing the patient’s chromosomes back to a balanced state.

Strengths of Gene Addition:

Introduction of Therapeutic Genes: Gene addition addresses epilepsy by adding genes that modulate neuronal activity or correct genetic defects.

Customized Treatment: Enables a customized technique by tailoring therapeutic genes to the patient’s unique genetic profile.

Neuroprotective Factors: Potential to introduce genes generating neuroprotective elements, safeguarding neurons during seizures.

Advancements in Gene Therapy: Offers new possibilities for dealing with epilepsy at the genetic stage, contributing to the evolution of gene therapy techniques.

Limitations of Gene Addition:

Precision and Specificity: Achieving particular focus on affected brain regions without off-target consequences is difficult.

Immune Responses: Introducing foreign genetic material might also cause immune responses, impacting remedy efficacy.

Long-Term Safety: Ensuring the protection of gene addition treatment options over the long term, including the capacity for unintentional consequences, is a crucial problem.

Delivery Challenges: Efficient and targeted delivery of healing genes to the mind, overcoming the blood-brain barrier, poses demanding situations.

Gene Editing in Epilepsy

Gene editing is a groundbreaking attribute of gene therapy in itself. The method will take an abnormal cell and either remove it, modify it, or completely replace it with an efficient sequence of DNA. Similarly to gene therapy and its various methods, gene editing has techniques that continue to be clinically studied and improved. The most popular gene editing technique currently utilized today is CRISPR-Ca9. CRISPR-Ca9 is a genetically engineered system that helps scientists target a specific stretch of genetic code and edit DNA sequences with high precision. Genetic epilepsy is treated by directly altering a patient’s genes without the need for replacement. Gene editing decreases the chances of a patient passing down a seizure-prone gene to their children and reduces the number of seizures experienced in the long run.

Strengths of Gene Editing

Targeted Correction: Precise correction of epilepsy-associated genetic mutations.

Customized Treatment: Enables a customized technique by tailoring therapeutic genes to the patient’s unique genetic profile.

Therapeutic Innovation: Potential creation of progressive treatment plans by modifying genes involved in neuronal hobby.

Hereditary Modification: Potential prevention of transmission of epilepsy-associated genetic mutations to destiny generations.

Potential Long-Term Solutions: Addresses the root genetic causes for sustained therapeutic effects.

Treatment of Drug-Resistant Cases: Offering opportunity techniques for individuals with drug-resistant epilepsy or specific genetic editions.

Limitations of Gene Editing

Precision and Off-Target Effects: Achieving specific edits without accidental outcomes is essential to preventing unpredictable consequences.

Immune Responses: The introduction of edited genetic material may additionally trigger immune responses, probably impacting the therapy’s effectiveness.

Long-Term Safety Concerns: Ensuring the safety of gene-enhancing treatment options over the years, together with capacity unintended effects, is an important consideration.

Delivery Challenges: Efficient and centered delivery of gene-enhancing gear to the mind faces obstacles, along with the blood-brain barrier.

Conclusion

Gene therapy, encompassing gene addition and genetic editing, holds substantial promise as a viable treatment avenue for genetic epilepsy patients. The ability to introduce therapeutic genes, correct genetic defects precisely, and potentially offer long-term solutions marks significant strides in precision medicine. However, challenges such as the complexity of epilepsy, precision issues, potential immune responses, ethical considerations, and regulatory approval processes must be diligently navigated. The strengths of gene therapy lie in its targeted correction, customized treatments, and innovative potential, particularly in addressing drug-resistant cases. While the field has seen groundbreaking developments, ongoing research is essential to refine techniques, address limitations, and ensure the safety and efficacy of gene therapy approaches for epilepsy.

References:

Carpenter, J. C., & Lignani, G. (2021). Gene Editing and Modulation: the Holy Grail for the Genetic Epilepsies? Neurotherapeutics, 18(3), 1515–1523. https://doi.org/10.1007/s13311-021-01081-y

Gene-therapy history | GenePossibilities. (n.d.). Www.genepossibilities.com. Retrieved November 21, 2023, from: https://www.genepossibilities.com/gene-therapy-history

McCain, J. (2005). The Future of Gene Therapy. Biotechnology Healthcare, 2(3), 52–60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3564347/#:~:text=At%20first%20it% 20was%20thought

Riban, V., Fitzsimons, H. L., & During, M. J. (2009). Gene therapy in epilepsy. Epilepsia, 50(1), 24–32. https://doi.org/10.1111/j.1528-1167.2008.01743.x

What is gene therapy?: MedlinePlus Genetics. (2022, February 28). Medlineplus.gov. https://medlineplus.gov/genetics/understanding/therapy/genetherapy/#:~:text=Gene% 20therapy%20techniques%20allow%20doctors

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