Gene Therapy and Vision Restoration

Molly's Condition and Diagnosis

• Molly's Early Signs: Vision impairment noticed during infancy. Symptoms of an inherited disease likely leading to blindness by adulthood.
• Genetic Cause: Mutation in genetic instructions for a protein in her eyes.

Introduction to Gene Therapy

• Historical Context: Since decoding the genetic code, biologists envisioned curing diseases like Molly’s with genetic knowledge.
• Gene Therapy: Developed from lab research to a medical revolution.

Fundamentals of Gene Therapy

• Genes and Proteins: Genes produce proteins needed for cell functions. Mutations lead to faulty or absent proteins.
• Gene Therapy Principle: Provides cells with corrected gene copies to produce functional proteins.
• Benefits: Treats diseases at their root, stopping them by altering cell instructions.

McGuire and Bennett's Work

• Background: McGuire focused on eyes and Bennett on genetics; collaborated since the 1980s.
• Research Focus: Treating blindness with genes, particularly in the retina.
  • Retina: Converts light to signals sent to the brain.
• Challenges: Lack of gene identification, cloning technology, and established procedures.

Viral Vector Technology

• Viral Gene Delivery: Viruses used to deliver corrective genes to targeted cells.
  • How It Works: Harmful and replicative genes removed; corrective gene inserted.
  • Injection: Modified viruses injected into targeted tissues, delivering the corrective gene.

Animal Testing

• Mouse Models: Initial tests on mice eyes, proving viral delivery of genes.
• Large Animal Models: Used Briard Shepherds with human-comparable eye size and similar blindness condition.
  • Results: Successful sight restoration in dogs, paving the way for human trials.

Challenges and Setbacks

• Human Trials and Tragedy: 1999 incident where patient died due to immune reaction halted gene therapy progress.
• Perseverance: Despite setbacks, researchers like Bennett and High continued developing safe procedures.

Human Trials

• Clinical Trials: Adapted virus delivery for safe human use; first trials in 2007.
• Molly's Treatment: Entered trial, successfully restored partial vision allowing for activities like seeing the moon.

Broader Implications

• Impact on Patients: Over 40 patients treated with significant improvements.
• FDA Approval: 2017 recommendation for approval of RPE65 gene therapy.
• Future Prospects: Success with RPE65 gene therapy helps advance treatments for other inherited diseases.

Conclusion

• Collaboration in Science: Success attributed to multi-disciplinary efforts and collaboration.
• Hope for the Future: Gene therapy shows promise for treating various genetic conditions, bringing new hope to patients like Molly.