Skip to main content

Enabling Novel Treatments for Nervous System Disorders by Improving Methods for Traversing the Blood–Brain Barrier Proceedings of a Workshop (2018) / Chapter Skim
Currently Skimming:

4 Regulatory Considerations for Drugs That Traverse the BloodBrain Barrier
Pages 25-30

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.


From page 25...
... . • Since animal models may have limited reliability as tools for assessing human toxicity, multiple in vivo and in vitro studies may be required to establish a starting dose, followed by incremental dose increases (Chiocca, Whittaker)
Read the entire page →
From page 26...
... To ensure the safety of chronic dosing, more data will be needed. With regard to immunogenicity, he recalled that although checkpoint inhibitors appeared to be safe in preclinical models, when they were introduced in the clinic, patients died as a result of highlevel immune activation that caused excessive, systemic autoimmune responses.
Read the entire page →
From page 27...
... In addition to safety, Francesca Bosetti reminded workshop participants to also keep efficacy in mind. She said that preclinical, translational programs at the National Institute of Neurological Disorders and Stroke try to mimic as closely as possible the practices used in clinical trials, keeping in mind that outcome measures in clinical studies should reflect outcome measures that are used as end points in clinical trials.
Read the entire page →
From page 28...
... Antonio Chiocca, Harvey Cushing Professor of Neurosurgery at Harvard Medical School, expressed concern about using animal models for safety assessments, since animal models may have limited reliability as tools for assessing human toxicity. However, Whittaker commented that for first-in-human trials the only safety data available may have come from animal studies.
Read the entire page →
From page 29...
... A bigger challenge in terms of conducting a clinical trial for an orphan indication is enrollment and how to deal with heterogeneity when the number of trial participants is small, he said. Alexandra Golby said that she and her colleagues are in discussions with FDA to try to put together the first clinical trial of focused ultrasound with microbubbles to disrupt the BBB and deliver drugs.
Read the entire page →

Key Terms

  • focused ultrasound
  • clinical trials
  • safety studies
  • safety threshold
  • clinical studies

  • clinical trial
  • incremental dose
  • assessing human
  • regulatory challenges
  • matthew whittaker

  • preclinical models
  • acceptable safety
  • cognitive effects
  • review team
  • trial participants

  • dose increases
  • human toxicity
  • limited reliability
  • nonrodent species
  • outcome measures

  • effect level
  • trial design
  • appropriate clinical
  • patel noted
  • preclinical studies

  • applied regulatory
  • adequate safety
  • nonclinical studies
  • vikram patel
  • additional regulatory


    • This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
    More information on Chapter Skim is available.