Pharmacological approaches to tackle NCLs

Area of Science:

• Neuroscience and Genetics
• Lysosomal Storage Disorders
• Rare Genetic Diseases

Background:

• Neuronal ceroid lipofuscinoses, or Batten disease, are rare monogenic disorders characterized by progressive neurological decline.
• Caused by mutations in at least 13 genes, these diseases involve lysosomal storage material accumulation.
• Therapeutic development faces hurdles including limited physiopathology knowledge, small patient cohorts, and low commercial interest.

Purpose of the Study:

• To review emerging therapies for Batten disease, focusing on small-molecule identification.
• To highlight the role of high-throughput screening (HTS) and high-content screening (HCS) in accelerating drug discovery.
• To emphasize the potential of drug repurposing for Batten disease.

Main Methods:

• Review of current and emerging therapeutic strategies for Batten disease.
• Discussion of advancements in HTS and HCS using cell-based assays, automation, and imaging analysis.
• Exploration of drug repurposing approaches for identifying existing compounds for Batten disease treatment.

Main Results:

• HTS and HCS enable rapid screening of numerous compounds.
• These screening methods are particularly effective for drug repurposing in rare diseases like Batten disease.
• Drug repurposing significantly reduces the time and resources required for clinical translation.

Conclusions:

• Small-molecule therapies identified via HTS/HCS represent a promising therapeutic avenue for Batten disease.
• Drug repurposing accelerates the development of treatments by utilizing compounds already tested in humans.
• Technological advancements in screening are crucial for overcoming therapeutic development challenges in rare genetic disorders.