Aim of the project: Development and testing of an antisense oligonucleotide (AON) therapy for Dutch-type Cerebral Amyloid Angiopathy (D-CAA)
This project involves the development of an antisense oligonucleotide (AON) therapy for SCA3, in which the toxicity of the disease-causing protein ataxin-3 is reduced by AON-induced exon skipping. The efficacy and specificity of the AON treatment is investigated in neuronally differentiated induced pluripotent stem cells and a mouse model.
In partnership with ProQR, this project focuses on ways to alter toxicity of the mutant huntingtin protein by removing the hotspot of cleavage sites via exon skipping in the HTT gene, in animal and human iPSC organoid models.
The aim of the project is to develop a new antisense oligonucleotide (AON) therapy for Alzheimer’s disease (AD) and Dutch-type cerebral amyloid angiopathy (D-CAA) by using an exon skipping approach to decrease the forming of amyloid-beta. The AON will be tested in control and patient-derived neuronally differentiated induced pluripotent stem (iPS) cells and in a mouse model.
Our main goal is to develop an AON-based therapy for SCA1 patients. In a multidisciplinary consortium consisting of committed patients and families, clinicians, biomedical scientists, and a biotechnology company we will validate the lead molecule, perform toxicology studies, and conduct a natural history and biomarker discovery study to determine the best read-out parameters for the phase 1 clinical trial, conducted within this project.
The Dutch Center for RNA Therapeutics (DCRT) will focus on RNA therapy for patients for whom local treatment of the affected tissue is possible. The treatment targets progressive eye, muscle and brain diseases. The focus is on genetic diseases and mutations, which are so rare that pharmaceutical companies have no interest to invest in developing treatments. The DCRT will be the first centre in Europe to develop RNA therapy for such rare diseases.
Investigate iron accumulating properties of human iPSC-derived microglia-like cells (iPSC-MG) and study differences between control- and AD derived iPSC-MGs.