A recent review in Drug Discovery Today explores alternative approaches to preclinical drug discovery, using hereditary spastic paraplegias (HSPs) as a case study. The authors discuss how different therapeutic strategies, including gene therapy, de novo small-molecule discovery, and drug repurposing, can be applied to rare genetic diseases.

The review also examines the role of computational approaches in accelerating these programs. In particular, the authors highlight tools for pathogenic variant analysis, protein structure prediction, virtual screening, and experimental validation, while discussing the strengths and limitations of each approach. Successful case applications are used to illustrate how these methods can contribute to the development of new treatment strategies.

PUXANO’s contribution

PUXANO contributed to this work as part of the IAHSP Consortium, with PUXANO’s CEO Wouter Van Putte among the consortium members.

The collaboration highlights PUXANO’s involvement in applying structural biology and computational approaches to drug discovery for rare diseases. By combining genetic and clinical information with protein structure prediction, in silico screening, and experimental validation, these approaches can help identify and prioritize potential therapeutic strategies.

For rare diseases where conventional drug development can be particularly challenging, integrating structural biology, computational modelling, and experimental approaches offers an opportunity to make preclinical drug discovery more accessible and efficient.

Read the full review: Preclinical alternative drug discovery programs for monogenic rare diseases. Should small molecules or gene therapy be used? The case of hereditary spastic paraplegias, Drug Discovery Today (2024).