Genes as Medicine | HHMI BioInteractive video

Summary

The script narrates the groundbreaking journey of gene therapy from a concept to a medical revolution, focusing on the story of Molly Troxel, who was diagnosed with an inherited form of blindness. It details the scientific breakthroughs, the challenges faced, and the eventual success in restoring sight in Molly and others through the pioneering work of Jean Bennett and Albert Maguire. The narrative illustrates the power of genetic research and collaboration in transforming lives.

Takeaways

• 👶 Laura and Ryan Troxel received the heartbreaking news that their daughter Molly had an inherited disease that would likely cause her to lose her sight by adulthood.
• 🧬 Molly's blindness was caused by a mutation in the RPE65 gene, which is responsible for producing a protein crucial for the function of photoreceptors in the retina.
• 🔬 Gene therapy, a concept that involves altering the genetic instructions within cells, was seen as a potential cure for diseases like Molly's since the discovery of the genetic code.
• 🐕 Jean Bennett and Albert Maguire used Briard shepherds, dogs with a similar genetic condition to human Leber amaurosis, to develop and test gene therapy for blindness.
• 💉 The principle of gene therapy involves using modified viruses to deliver a corrected copy of a mutated gene into cells, allowing them to produce the necessary functional protein.
• 👁️ The Briard shepherds served as an ideal large animal model for testing gene therapy due to their eye size being comparable to humans and sharing the same genetic condition.
• 🚫 The field of gene therapy faced a significant setback with the death of Jesse Gelsinger during a gene therapy trial for a liver disease, causing a halt in clinical trials and a loss of funding.
• 🔄 Despite setbacks, Bennett and Maguire continued their research, successfully restoring sight in Briard shepherds with the RPE65 mutation, marking a breakthrough in gene therapy.
• 👩‍⚕️ Katherine High's interest in Bennett's work led to the initiation of human clinical trials for RPE65 gene therapy, which took years to adapt for safety and efficacy in humans.
• 🌟 Molly Troxel, at the age of 11, participated in a gene therapy clinical trial, which resulted in her being able to see the moon and stars, significantly improving her quality of life.
• 🛑 The success of RPE65 gene therapy in clinical trials brought the treatment of other inherited diseases closer to reality, highlighting the importance of collaboration and persistence in scientific research.

Q & A

What was the initial indication that Molly had a vision impairment?

Molly's mother, Laura, noticed that while breastfeeding, Molly would look away from her to see a light elsewhere in the room.

What was the devastating news that Laura and Ryan Troxel received about their daughter Molly?

Molly was diagnosed with an inherited disease that would likely cause her to lose her remaining sight by adulthood.

How is Molly's blindness linked to her genetic makeup?

Molly's blindness is due to a mutation in the genetic instructions for a protein in her eyes, which is an inherited condition.

What is the fundamental principle of gene therapy as described in the script?

The principle of gene therapy is to provide cells with a corrected copy of the mutated gene that will produce a functional protein, treating the disease at its root.

Why were eyes considered a good target for developing a gene therapy?

Eyes are easy to access, and having two eyes means that in an experiment, one can be treated while the other acts as a control.

How do viruses play a role in gene therapy?

Viruses are used in gene therapy because they have evolved to move DNA or RNA across cell membranes effectively. Scientists use modified viruses to deliver corrective genes into cells.

What was the significance of the Briard shepherd dogs in the development of gene therapy for blindness?

Briard shepherd dogs have eyes about the size of humans and suffer from the same form of blindness as the leading cause of childhood blindness, making them an ideal model for testing gene therapy.

What was the tragic event that occurred during a gene therapy trial in 1999, and how did it affect the field?

Jesse Gelsinger died after his immune system reacted to the viral vector used in the gene therapy trial, causing a halt in gene therapy research and a withdrawal of interest and funding.

How did the success in treating Briard shepherd dogs with gene therapy influence the decision to proceed with human trials?

The successful restoration of sight in Briard shepherd dogs provided the first hope and proof of concept that gene therapy could be effective in humans, leading to the decision to proceed with human trials.

What was the outcome of Molly Troxel's gene therapy treatment, and how did it affect her life?

After the gene therapy treatment, Molly was able to see the moon and stars, which significantly improved her quality of life and independence, even though she still appears visually impaired to outsiders.

What was the historical milestone achieved by RPE65 gene therapy in 2017?

In 2017, RPE65 gene therapy was recommended for approval by a panel of the Food and Drug Administration for the treatment of congenital Leber amaurosis, marking a significant step forward in gene therapy treatments.