HNRNPU-NDD Registry
Research type
Research Study
Full title
HNRNPU-related neurodevelopmental disorder: creating an international registry and natural history study.
IRAS ID
314583
Contact name
Meena Balasubramanian
Contact email
Sponsor organisation
Sheffield Children's NHS Foundation Trust
Duration of Study in the UK
3 years, 3 months, 1 days
Research summary
Background: Over 95% of patients with faults within HNRNPU gene develop seizures; majority do not respond to standard anti-epileptic medications. Therefore, there is an overwhelming need to develop better treatments. We published the largest clinical dataset on HNRNPU and work closely with HNRNPU patient support group. We want to develop an international registry of patients with hnrnpu and collect natural history and longitudanal data. The short term goal is to deliver HNRNPU protein to restore normal functions to affected cells in HNRNPU syndrome. The long term aim is to develop a ‘cure’ i.e. gene therapy where we deliver the correct form of HNRNPU to the brain providing a single dose, long term treatment.
Approach: We will be collecting clinical and genotypic data on all participants. In addition, using cells (blood and skin cells) obtained from HNRNPU patients, we will
transform patient cells into firstly stem and then nerve cells (neurons), characterise their properties using cutting-edge genomics technologies and measure activity of specific receptors, known to be dysregulated. We will then develop gene therapy tools to replace missing HNRNPU in patient cells to see whether we can restore normal HNRNPU levels and neuronal function.Outcomes: This approach will be applicable to other forms of epilepsy resulting from reduced protein in brain due to a specific gene defect. This form of gene therapy has already been clinically approved for treatment in diseases such as spinal muscular atrophy (Zolgensma), so this would be new application of an established technology.
Impact: We hope to develop gene therapies which can be used to provide sustained single dose treatment for genetic forms of epilepsy including HNRNPU syndrome. This work is timely because Sheffield is one of only three UK gene therapy centres under construction, (£18 million investment), providing a clear route from our bench work to clinic.
REC name
North East - Newcastle & North Tyneside 2 Research Ethics Committee
REC reference
22/NE/0125
Date of REC Opinion
13 Dec 2022
REC opinion
Further Information Favourable Opinion