As her muscles weaken, Sabrina leans on her best friend for strength, support

AI News Q&A (Free Content)

Q1: What is the significance of the new gene therapy drug Tofersen for patients like Ms. Sabrina?

A1: Tofersen is a new gene therapy drug developed by Biogen to target the SOD1 gene, which is crucial for protecting cells from oxidative stress. For Ms. Sabrina, who carries a rare genetic variant in this gene, Tofersen works by reducing the accumulation of abnormal SOD1 protein that causes nerve cell death. Administered via spinal fluid, it offers hope for extending her lifespan by addressing the underlying genetic cause of her muscle weakness.

Q2: How does the exon skipping strategy contribute to the treatment of centronuclear myopathy (CNM)?

A2: Exon skipping strategies, such as the use of peptide-conjugated morpholinos, have shown promise in treating CNM by targeting the DNM2 gene. By downregulating DNM2 protein levels in muscle, this approach can rescue muscle force and reverse disease phenotypes in animal models. This method offers a potential translational approach for patients with DNM2 mutations and other forms of CNM.

Q3: Why is gene therapy considered a promising approach for treating muscular dystrophies?

A3: Gene therapy is promising for muscular dystrophies because it offers targeted treatment by addressing genetic mutations directly. For example, an efficient dual vector system can deliver gene fragments that reconstitute in affected tissues, potentially reversing muscle degeneration. This approach is particularly beneficial in cases where traditional gene delivery methods are not feasible.

Q4: What are the challenges associated with gene therapy for treating muscle-related disorders?

A4: Gene therapy for muscle-related disorders faces challenges such as ensuring safe and efficient gene delivery, avoiding immune responses, and achieving long-lasting effects. Additionally, not all gene therapies have been successful, as evidenced by some clinical trials showing toxicity in non-muscle tissues. Overcoming these hurdles is crucial for the successful application of gene therapy in muscle disorders.

Q5: How prevalent is the genetic variant targeted by Tofersen, and why is it significant?

A5: The genetic variant targeted by Tofersen in the SOD1 gene is rare, contributing to conditions like ALS with a prevalence of four to seven per 100,000 people globally. Despite its rarity, targeting this variant is significant because it directly addresses the molecular cause of nerve cell death, offering a tailored therapeutic approach for affected individuals.

Q6: What role does the SOD1 gene play in cellular processes, and how does Tofersen interact with it?

A6: The SOD1 gene is involved in protecting cells from oxidative stress by balancing free radicals and antioxidants. Tofersen interacts with this gene by reducing the accumulation of its abnormal protein products, which are toxic to nerve cells. This reduction helps to slow the progression of diseases associated with this genetic variant.

Q7: What advancements have been made in gene therapy for muscular dystrophy at the University of Rochester Medical Center?

A7: The University of Rochester Medical Center has developed a dual vector system for gene therapy, which efficiently delivers gene segments that recombine in affected tissues. This advancement allows for the treatment of muscular dystrophies by overcoming size limitations in gene delivery, facilitating potential therapeutic applications for various genetic disorders.

References:

• Gene therapy - https://en.wikipedia.org/wiki/Gene_therapy
• Exon skipping peptide-conjugated morpholinos downregulate dynamin 2 to rescue centronuclear myopathy - https://academic.oup.com/brain/article/148/9/2592/6568794
• As her muscles weaken, Sabrina leans on her best friend for strength, support - https://www.straitstimes.com/singapore/as-her-muscles-weaken-sabrina-leans-on-her-best-friend-for-strength-support
• New Discovery Enables Gene Therapy for Muscular Dystrophies, Other Disorders - https://www.urmc.rochester.edu/news/story/new-discovery-enables-gene-therapy-for-muscular-dystrophies-other-disorders