Preclinical alternative drug discovery programs for monogenic rare diseases. The case of hereditary spastic paraplegias.
Drug Discov Today
; : 104138, 2024 Aug 19.
Article
in En
| MEDLINE
| ID: mdl-39154774
ABSTRACT
Patients diagnosed with rare diseases and their and families search desperately to organize drug discovery campaigns. Alternative models that differ from default paradigms offer real opportunities. There are, however, no clear guidelines for the development of such models, which reduces success rates and raises costs. We address the main challenges in making the discovery of new preclinical treatments more accessible, using rare hereditary paraplegia as a paradigmatic case. First, we discuss the necessary expertise, and the patients' clinical and genetic data. Then, we revisit gene therapy, de novo drug development, and drug repurposing, discussing their applicability. Moreover, we explore a pool of recommended in silico tools for pathogenic variant and protein structure prediction, virtual screening, and experimental validation methods, discussing their strengths and weaknesses. Finally, we focus on successful case applications.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Drug Discov Today
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2024
Document type:
Article
Affiliation country:
Italia
Country of publication:
Reino Unido