Ricardo Dolmetsch – Precision Medicine for Rare Childhood Diseases: Stanford Childx Conference

TL;DR

Developing drugs for neurodevelopmental disorders is challenging due to complex diseases, limited preclinical models, safety concerns, drug delivery to the brain, and difficulty measuring outcomes in clinical trials.

Transcript

[MUSIC PLAYING] So our next speaker on stage is going to be Ricardo Dolmetsch. I've known Ricardo for many years now. He's been traveling back and forth between the East coast and the West coast. He did his PhD here. Then did his post-doc in Boston. Then came back as a faculty here in Neuroscience. And then he's been recently recruited as the globa... Read More

Key Insights

• 😘 Drug companies in neuroscience face lower success rates and higher risks due to the complexity and heterogeneity of neurodevelopmental diseases.
• 👍 Mouse pharmacological models, traditionally used in preclinical drug development, have proven ineffective in predicting human drug response.
• 🧠 Developing safe drugs for the brain poses unique challenges, as long-term safety and effective drug delivery to the brain are critical.
• 🧑‍🏭 Measuring outcomes in clinical trials for neurodevelopmental disorders is complicated by the diversity of patient populations and the impact of external factors.
• 🥺 Narrowing down patient populations and focusing on genetically defined disorders may lead to more successful drug development.
• ❓ Innovative approaches, such as creating disease-specific in vitro models using stem cells, offer promise in understanding disease mechanisms and optimizing drug development.

Questions & Answers

Q: Why have drug companies been unsuccessful in neuroscience, according to recent studies?

Recent studies have shown that drug companies in neuroscience have a lower success rate, leading to many companies exiting the field. This is due to the complexity of neurodevelopmental diseases like autism and depression, which are not single diseases but a combination of different disorders.

Q: How have preclinical models and assays hindered drug development in neuroscience?

Historically, drug development in neuroscience has relied heavily on mouse pharmacological models. However, after significant investments, it has been found that these models do not accurately predict drug efficacy in humans. This lack of reliable preclinical models has slowed down drug development in neuroscience.

Q: Why is developing safe drugs for the brain particularly challenging?

In the field of neuroscience, drugs often need to be extremely safe and have long-term effects since they are administered to patients for extended periods. The tolerance for risk has decreased, making it difficult to develop drugs that are both effective and safe for the brain.

Q: How do challenges in measuring outcomes complicate clinical trials for neurodevelopmental disorders?

Measuring outcomes in neurodevelopmental disorders, such as mood, attention, and memory, is challenging due to the heterogeneity of patient populations and the influence of external factors like coffee consumption or sleep quality. Clinical trial designs need to be improved to address these difficulties and minimize the placebo effect.

Summary & Key Takeaways

• Ricardo Dolmetsch, the global head of neuroscience at Novartis, discusses the challenges in developing treatments for neurodevelopmental disorders.

• Drug companies have struggled in neuroscience due to the complexity and heterogeneity of diseases like autism and depression.

• Preclinical models based on mouse pharmacological models have not been effective in predicting drug efficacy in humans.

• Developing safe drugs for the brain and measuring outcomes in clinical trials present additional challenges.