Drug discovery and development for spinal muscular atrophy: lessons from screening approaches and future challenges for clinical development.
Future Med Chem
; 2(9): 1429-40, 2010 Sep.
Article
en En
| MEDLINE
| ID: mdl-21426138
ABSTRACT
Spinal muscular atrophy (SMA) is a progressive pediatric neuromuscular disease. Because disease severity is related to survival motor neuron (SMN) protein levels, increasing SMN production from the SMN2 gene has been a major SMA drug-discovery strategy. Cell-based assays using neuronal cell lines and cells from SMA patients have identified compounds that can increase SMN protein expression. Our experience of using such an assay signaled potential risks to be avoided through the use of appropriate secondary assays. In addition to the 'SMN2' approach, compensating for decreased SMN protein or neuroprotection are also potential SMA drug-discovery strategies. SMA clinical trials are now a reality; however, trial design in a slowly progressing rare disease such as SMA will present an interesting future challenge.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Atrofia Muscular Espinal
/
Descubrimiento de Drogas
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Límite:
Humans
Idioma:
En
Revista:
Future Med Chem
Año:
2010
Tipo del documento:
Article
País de afiliación:
Francia