Whispers of Tomorrow: Gene Therapy’s Quest to Silence Neurodegeneration

Limited treatment options are available for neurodegenerative diseases (NDs), leaving millions of patients and their families worldwide to endure these conditions while struggling to access essential medical care. The troubling predicament of these individuals has pushed scientists to explore new therapeutic avenues that may offer new hope to these patients.

Neurodegenerative diseases diminish patients’ quality of life and are characterized by the loss of structure and function of neurons, the primary cells of the nervous system. The effects of this loss depend on the type of neuron and its location in the brain. For instance, patients with Parkinson’s disease (PD) gradually lose their motor abilities, whereas patients with Alzheimer’s disease face cognitive disruption.

Unfortunately, not only are treatments for these diseases limited, but existing options also tend to target symptom relief rather than the diseases’ chemical and biological root causes. In addition, the blood-brain barrier (BBB), a highly selective membrane that filters molecules and ions from entering the brain, prevents some existing drugs from reaching their destination, blocking the effects of the treatment altogether (Sudhakar and Richardson). Therefore, there is a pressing need for new innovative procedures, and gene therapy offers a possible lasting solution to this problem.

Gene therapy refers to the introduction of a therapeutic gene–whether it be a synthetic DNA molecule made by researchers or an extracted gene naturally found in another organism– to replace a harmful one in an organism’s DNA (Papanikolaou and Bosio). When this gene is introduced into a cell, it is expressed by cell machinery, leading to beneficial effects. In the case of NDs, genes could be introduced that help combat neuron degeneration, protecting the patient from further genetic mutations or chemical dysregulations by changing its core genetic makeup.

These therapies have already shown success in treating other conditions. As of 2024, five gene therapies for rare diseases have been approved by the U.S. Food and Drug Administration. These include treatments for a blood hemoglobin disorder (Beta-thalassemia), a brain condition that damages the protective myelin sheaths of neurons (adrenoleukodystrophy), and a disorder characterized by lack of blood clotting (hemophilia A) (Mullard 87). Although it may seem unfeasible, gene therapy is a very real technology that is already in use today.

But how are therapeutic genes actually transported to their targets? A common method to carry therapeutic genes are viruses. Viruses can first be modified so that they are no longer harmful to the health of the host organism. This virus is then loaded with the desired gene and introduced surgically or non-invasively to deliver the gene to target cells (Li et al.). Efficiently implementing this delivery technique ensures the gene therapy reaches the target cells, as opposed to other methods where the BBB or the cell membrane of neurons could block it.

To confirm the safety and efficacy of these gene therapies for the treatment of NDs, clinical trials are absolutely critical. Trials have been conducted on a range of NDs, but one disease of particular interest has been Parkinson’s disease, where neurons that produce the chemical dopamine, essential for movement control, decay in the brain. The majority of the trials, in animals and humans, focus on introducing a gene that codes for enzymes that control the production of dopamine. The goal is to combat the effects of losing neurons that produce the chemical (Muramatsu et al). The results from the study by Muramatsu et al. were promising, showing that participants’ motor performance improved following the genetic treatment. Although the small number of participants —six individuals— was a limitation of the study, the results show that the potential of gene therapy should be taken seriously and tested further.

Gene therapy holds significant promise in becoming a solution for neurodegenerative diseases, considering the current absence of curative treatments. Similar to every novel procedure, gene therapy faces challenges that include its accuracy in introducing a gene into the patient’s genome and potential disruption of other genes (Papanikolaou and Bosio). Nonetheless, this should not stop its development. With further advances in these procedures and genetic engineering techniques, gene therapy could become the gold-standard treatment and help millions of patients globally. There should be great effort placed into developing better techniques for the delivery of these systems to ensure their accuracy and efficiency. After all, gene therapy may hold life-saving and life-changing potential for those afflicted by neurodegenerative diseases.

References

1. Li, Leyao, et al. “Advances in recombinant adeno-associated virus vectors for neurodegenerative diseases.” Biomedicines, vol. 11, no. 10, 8 Oct. 2023, p. 2725, https://doi.org/10.3390/biomedicines11102725.

2. Mullard, Asher. “2022 FDA approvals.” Nature Reviews Drug Discovery, vol. 22, no. 2, 3 Jan. 2023, pp. 83–88, https://doi.org/10.1038/d41573-023-00001-3.

3. Muramatsu, Shin-ichi, et al. “A phase I study of aromatic L-amino acid decarboxylase gene therapy for parkinson’s disease.” Molecular Therapy, vol. 18, no. 9, Sept. 2010, pp. 1731–1735, https://doi.org/10.1038/mt.2010.135.

4. Papanikolaou, Eleni, and Andreas Bosio. “The Promise and the Hope of Gene Therapy.” Frontiers in Genome Editing, vol. 3, 24 Mar. 2021, https://doi.org/10.3389/fgeed.2021.618346.

5. Sudhakar, Vivek, and R. Mark Richardson. “Gene therapy for Neurodegenerative Diseases.” Neurotherapeutics, vol. 16, no. 1, 15 Jan. 2019, pp. 166–175, https://doi.org/10.1007/s13311-018-00694-0.