Gene Therapy -- The time is now: Nick Leschly at TEDxBoston

Summary

The speaker shares a deeply personal journey in the field of gene therapy, starting with the heart-wrenching story of Ethan, a young boy with a fatal genetic disorder called ALD. He transitions to the innovative strides in gene therapy, using stem cells to combat diseases like ALD and hemophilia, demonstrating the potential to cure or transform lives. The talk concludes with a call to action, urging stakeholders to address the challenges in regulatory approval and payer perspectives to ensure life-saving treatments reach patients in need.

Takeaways

• 🌟 The speaker starts with an introduction that highlights the inspiration behind his work, emphasizing the joy of family and the dream of transforming lives through gene therapy.
• 🏥 The narrative focuses on a disease called Adrenoleukodystrophy (ALD), which is portrayed as a genetic death sentence for children, with a deeply emotional story about a child named Ethan.
• 🧬 The script explains the role of a specific cell in the brain, the microglial cell, which is affected in ALD and leads to the accumulation of very long-chain fatty acids, causing severe neurological issues.
• 💉 The speaker discusses the concept of gene therapy, aiming to cure or transform the lives of children with genetic disorders, using a 'Buck Rogers' futuristic analogy.
• 🛠️ The process of gene therapy is described in detail, involving the creation of a virus to deliver a therapeutic gene into blood stem cells, which can then produce the necessary proteins to combat the disease.
• 🔬 The script introduces the audience to the scientific process of gene therapy, including the use of 293T cells to manufacture the components of the therapeutic virus.
• 🧪 The video shown during the talk illustrates the complex steps of gene therapy, from the creation of the virus to its interaction with blood stem cells outside the body.
• 🩺 The potential of gene therapy is demonstrated through the transformational effects on patients with ALD and other genetic disorders, such as hemophilia.
• 💼 The speaker raises concerns about the readiness of the regulatory system, payers, and the industry to embrace and support the development and application of gene therapies.
• 🤔 The script concludes with a call to action, urging stakeholders to find a balance between scientific advancement and the practical challenges of delivering gene therapies to patients.
• 🌱 The overarching message is one of hope and the potential for gene therapy to provide a 'bluebird day' for children suffering from previously untreatable genetic conditions.

Q & A

What is the speaker's motivation for starting his day with a smile?

The speaker is motivated by two reasons: having a supportive family with an inspirational wife and five daughters, and working at Bluebird where he gets to work on a therapy that could potentially cure or transform the life of a child with a genetic disease.

What is the condition called Adrenoleukodystrophy (ALD)?

Adrenoleukodystrophy (ALD) is a genetic disorder that affects the myelin sheath, which is the protective covering of nerve fibers in the brain. It can be life-threatening and was depicted in the movie 'Lorenzo's Oil'.

What is the significance of the brain scan shown in the script?

The brain scan is of a seven-year-old child with ALD. The white areas in the scan indicate demyelination, which is the breakdown of the myelin sheath, and the buildup of very long-chain fatty acids, which are harmful to the brain.

Who is Ethan, and what is his connection to the speaker's story?

Ethan was a nine-year-old boy, the son of a friend of the speaker and a fellow CEO in the industry. Ethan was diagnosed with ALD too late, and his story serves as a stark reminder of the urgency and importance of the work the speaker is involved in.

What is the role of the blood stem cell in gene therapy?

The blood stem cell, also known as the 'Mother cell,' is crucial in gene therapy because it can turn into various types of cells, including the microglial cell affected in ALD. Gene therapy aims to either replace these cells or fix the genetic issue within them.

What is the process of creating a gene therapy treatment as described in the script?

The process involves creating a viral vector in cellular manufacturing plant cells, which includes the therapeutic piece of RNA that encodes for the broken gene. This vector is then used to infect and modify the patient's blood stem cells outside the body, integrating the new gene into the cells' DNA, which are then reintroduced into the patient.

What is the challenge the speaker identifies in bringing gene therapy treatments to market?

The challenge lies in balancing the readiness of the regulatory system, societal acceptance, and the understanding of value by payers. The current system may not be adequately prepared to handle the transformative nature of gene therapies and their long-term benefits.

What is the significance of the barcode on the virus in gene therapy?

The barcode on the virus allows scientists to track every single blood molecule that is made with the therapy. This helps in understanding the effectiveness of the treatment and how it can be optimized for individual patients.

What is the speaker's view on the current balance between scientific advancement and stakeholder readiness?

The speaker believes that the balance is skewed and not quite right. He suggests that there is a gap between the readiness of scientific advancements and the readiness of stakeholders, which could potentially lead to patients not receiving life-saving treatments in time.

What is the term 'bluebird day' and what does it represent?

The term 'bluebird day' is used by the speaker's workplace to represent the ideal day for every child, emphasizing the goal of providing every child with the opportunity to have a day free from the burdens of their disease.

How does the speaker describe the impact of gene therapy on patients with genetic diseases?

The speaker describes the impact as transformative, with the potential to cure or dramatically improve the quality of life for patients with genetic diseases. He cites examples of patients with ALD and other diseases who have seen significant improvements after gene therapy.