Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL): Immunotherapy and Cell Therapy approaches

TL;DR

This paper reviews current and emerging therapeutic strategies for CADASIL, including gene editing, cell therapy, and immunotherapy, highlighting recent advances, clinical trials, and the potential for disease modification.

Contribution

It provides a comprehensive overview of novel therapeutic approaches and recent research developments for CADASIL, emphasizing translational potential and experimental models.

Findings

Advances in gene editing and cell therapies for CADASIL

Ongoing clinical trials for novel interventions

Potential for disease-modifying treatments

Abstract

This article focuses on current and emerging therapeutics for CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy). CADASIL is an inherited vascular disease that impairs blood flow in the small cerebral vessels of the brain, leading to strokes and other neurological deficits. The disease is caused by a mutation in the NOTCH3 gene located on chromosome 19. NOTCH3 encodes a transmembrane receptor expressed on vascular smooth muscle cells. In CADASIL, mutations in the NOTCH3 gene lead to the accumulation and deposition of the receptor, affecting the number of cysteine residues in its extracellular domain. These mutations result in the loss or gain of a cysteine residue within the epidermal growth factor-like repeat (EGFr) domains of the NOTCH protein. Beyond traditional symptomatic treatments for stroke, this work highlights advances in disease modifying approaches including gene editing, cell therapies, and immune-based interventions aimed at altering the course of CADASIL. It also examines ongoing clinical trials and recent patents related to these novel strategies. In addition to summarizing diagnostic methods and molecular mechanisms, the article emphasizes the translational potential of current research and the experimental models driving therapeutic development. The goal is to offer a comprehensive overview of CADASIL and emerging interventions that hold promise for improving long-term outcomes.