Guest Column | September 5, 2023

How Can We Approach Cell And Gene Therapy To Treat MS?

By AmbreƩn Zaman-Riaz, MBBCH, MPA, Uppshot Lifesciences

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Multiple sclerosis (MS) is a chronic neurological disorder that affects the central nervous system (CNS), which includes the brain and spinal cord. It is characterized by a broad range of symptoms that result from the immune system mistakenly attacking the protective covering of nerve fibers, known as myelin. This immune attack, called demyelination, disrupts the normal flow of electrical impulses along nerve fibers and can lead to neurological symptoms such as loss of vision in an eye, loss of power in an arm or leg, or a rising sense of numbness in the legs. Other symptoms of MS include fatigue, depression, spasms, incontinence issues, sexual dysfunction, and walking difficulties. The usual approach to management and treatment involves anti-inflammatory drugs, chemotherapy, and immunosuppressive drugs.

Lately, genome therapy is emerging as a breakthrough treatment option for MS patients. However, genome therapy for MS is still mainly in the experimental and preclinical stages. Researchers are working to understand better the genetic and molecular mechanisms underlying MS and how they might be targeted through gene-based interventions. Of course, clinical trials must assess the safety and efficacy of any potential genome therapy approaches before they can become established treatments, but let’s look at some ways that cell and genome therapy hold potential for treating MS.

Potential Methods For Cell And Genome Therapy To Treat MS

In the context of MS, research is underway to target specific genes associated with the immune response and inflammation that characterize the condition. Genome therapy could target the underlying genetic factors contributing to the development or progression of the disease. Some potential approaches to genome therapy for MS include:

  • Gene Editing: Techniques like CRISPR-Cas9 can be used to edit specific genes associated with MS to correct mutations or modulate their activity. For example, researchers aim to modify genes related to immune system regulation to prevent the autoimmune response that damages myelin.
  • Gene Delivery: One standard method for delivering therapeutic genes is through viral vectors, modified viruses that can carry specific genetic material into cells. These vectors can be engineered to target cells in the central nervous system and introduce therapeutic genes. Viral vectors or other delivery mechanisms could introduce therapeutic genes into patients' cells. These genes might produce factors that protect or repair myelin, regulate immune responses, or promote neural repair. 
  • Stem Cell Therapy: Stem cells could be engineered to differentiate into specific cell types to help repair damaged myelin or promote nerve cell survival. These modified stem cells could be transplanted into the patient's central nervous system.
  • Immunomodulation: Genome therapy could modify immune cells to reduce their attack on myelin, potentially mitigating the progression of MS. Regulatory T cells, or Tregs, are a subset of immune cells responsible for maintaining immune tolerance and preventing the immune system from attacking healthy tissues. Gene editing can be used to enhance the activity and function of Tregs. By modifying genes that control Treg development and function, researchers aim to increase the suppressive capabilities of these cells, thus dampening autoimmune responses.
  • Tolerizing the Immune System: Scientists are investigating ways to induce immune tolerance to myelin proteins.2 This involves using gene therapy to encourage the immune system to recognize myelin as a standard body component, reducing the immune system's attack.
  • Inhibiting Pro-inflammatory Genes: In autoimmune diseases like MS, specific genes promoting inflammation are overactive. Gene editing techniques can be employed to inhibit the expression of these pro-inflammatory genes. The immune system's attack on self-tissues can be mitigated by reducing the production of inflammatory molecules. One approach involves modifying the genes in immune cells to regulate their response to myelin and reduce the autoimmune attack on the central nervous system. By modulating the immune response, researchers hope to slow down or halt the progression of MS.
  • Promoting Myelin Repair: Gene therapy could introduce genes that promote the production and repair of myelin, the protective covering of nerve fibers. This could help to restore damaged myelin and improve nerve function.

Spotlight On CRISPR-Cas9 As A Tool Holding Promise

CRISPR-Cas9 is a powerful gene editing tool that allows scientists to precisely slice the DNA within cells and allow natural DNA repair processes to take over. In the context of MS, researchers might explore the following approaches using CRISPR-Cas9 or similar gene editing techniques:

  • Correcting Mutations: The genetic component in some cases of MS and certain genetic variations or mutations could contribute to an individual's susceptibility to the disease. CRISPR-Cas9 could correct these mutations or restore the normal function of affected genes. 
  • Modulating Immune Response: MS is characterized by an immune system attack on the myelin sheath surrounding nerve fibers. Gene therapy targets genes involved in immune system regulation by breaking the DNA and then taking advantage of cellular DNA repair pathways to modulate the activity of immune cells responsible for the autoimmune response that leads to the demyelination process. This helps prevent the immune system from mistakenly attacking the nervous system.
  • Enhancing Tolerance: Gene editing could promote immune tolerance, which is the immune system's ability to recognize and tolerate its tissues. Improving immune tolerance could reduce the autoimmune response in MS.
  • Promoting Remyelination: Genes that play a role in remyelination (rebuilding the myelin sheath) could be targeted to enhance repair mechanisms in the nervous system.

It's important to note that while the concept of using gene editing for MS is promising, several challenges need to be addressed. These challenges include the precision of gene editing, the delivery of the editing tools to the target cells in the central nervous system, potential off-target effects, and ethical considerations.

A personalized genome therapy approach for MS would involve tailoring treatments to individuals' unique genetic and molecular characteristics. This innovative approach can target the underlying causes of MS more effectively and precisely.


  1. Ceccaldi R., Rondinelli B., D'Andrea A.D. Repair pathway choices and consequences at the double-strand break. Trends Cell Biol. 2016;26:52–64. [PMC free article] [PubMed] [Google Scholar]
  2. A Tolerizing mRNA Vaccine against Autoimmunity?

About The Author:

Ambreén Zaman Riaz, MBBS, MPA, is a physician with an MPA from Harvard University. Her passion is solving problems in clinical medicine using AI and medical devices. She has global experience working as a healthcare consultant and social impact entrepreneur across multiple geographies.