Future Advances in Early Phase Clinical Development for Disease Modifying Therapies for Neurodegenerative Diseases

Medical Research Archives, vol. 10

Abstract

With aging populations in many countries, the prevalence of neurodegenerative diseases is expected to increase in the upcoming decades. Currently, no disease modifying therapies for these conditions exist. Advances in genetics and proteomics have identified novel druggable targets for neurodegenerative diseases. Compounds modulating these targets have recently entered clinical trials. These compounds can be orally administered small drug molecules, intravenously dosed antibodies, intrathecally injected antisense oligonucleotides (ASOs), gene therapies, stem cells or viral vectors. For the development of these compounds to be successful, multiple challenges have to be overcome. In this review we discuss advances in drug development for each of the major neurodegenerative diseases, which, when applied to early phase drug studies, increase the chance of successful clinical development. Here we will limit ourselves to: 1) the use of biomarkers for understanding target and pathway engagement at an early stage of development, 2) novel approaches for increasing blood-brain barrier penetration and 3) advances in understanding cerebrospinal fluid flow dynamics in relation to neurodegeneration and target site distribution for intrathecally administered compounds.

Authors 1

1. Geert Jan Groeneveld Aachen Centre for Human Drug Research (CHDR) Leiden Academical Medical Center

   Leiden University Medical Center · Centre for Human Drug Research

   Affiliation as printed

   Center for Human Drug Research, Leiden, The Netherlands; Leiden Academical Medical Center, Leiden, The Netherlands

   Center for Human Drug Research, Leiden, The Netherlands

   Leiden Academical Medical Center, Leiden, The Netherlands