Clinical Research: Phase 1 - Phase 4

Neurodegenerative Disease Research: Steps to a Successful Clinical Trial

Neurodegenerative disorders present some of the biggest challenges in planning and conducting clinical drug trials. Identifying strategies to proactively address or mitigate these challenges can help to ensure a successful trial.

Since the first drugs for neurodegenerative diseases (NDDs) were approved in the 1990s, an increasing number of disease- modifying therapies have been approved for multiple sclerosis (MS) and several symptomatic therapies have been approved for Alzheimer’s disease (AD). However, despite extensive research, none of these available treatments demonstrate the ability to halt neurodegeneration. Hence, developing drugs that can stop clinical progression remains the biggest challenge in NDD.

Recent advances in our understanding of the genetic, molecular, and cellular basis of neurodegeneration make this an exciting time for NDD research. As our understanding of NDD has increased, so has our understanding of how to conduct clinical trials to study them, including design, assessments, and biomarker use. For example, we know that patient profiling and adjudication of endpoints or adverse events of special interest can have a significant impact on drug development.

In this white paper, we explore the complexity of neurodegeneration and the operational challenges inherent in NDD studies. We also introduce strategies for mitigating these challenges to ensure a successful trial.

Complexity of neurodegenerative diseases

Neurodegenerative diseases are complex, both genetically and etiologically. Disease measurement can be vastly different based on biological variation, which presents a significant challenge to therapeutic development.

Developing representative phenotypes

Biological variability, clinical and radiological variability, and pathology and genetic heterogeneity all need to be considered when defining an NDD phenotype for a clinical trial. The same proteinopathy can present as different, distinct phenotypes and different proteinopathies can present with overlapping phenotypes. To further complicate matters, combination proteinopathies are a frequent occurrence.

We still do not know what triggers or accelerates neurodegeneration and spread of the disease, even in genetic NDDs. What we do know is that the pathobiology of NDD results in the distribution of different proteins in cells and subcellular structures, and we need to understand the overlap in the pathogenesis of different disorders to translate investigative compounds into effective therapies.

To read more, download the complete white paper by submitting the form on this page.