Cutting-edge Research Awarded BDSRA Australia’s 2020 Grants

The Batten Disease Support and Research Association (BDSRA) Australia has announced the winners of the 2020 Batten disease research grant program in Australia and New Zealand.

The purpose of the program is to support research in disease mechanisms, novel therapies, improvements in diagnosis, and treatment and disease management in Batten disease.

In the 2020 edition of the grant program, the project led by Anthony Cook, PhD, from the University of Tasmania, was awarded a AU$49,400 (about US$38,300) research grant.

Researchers used advanced techniques in stem cell biology and gene editing technology to develop a new human cell-based model of the disease. Previous research indicated that in this model, cells with variants in the CLN3 gene — the gene that is faulty in juvenile Batten disease — change how nerve cells communicate.

The goal of the project is to screen over 350 candidate molecules and identify potential new therapies for Batten disease caused by variants in the CLN3 gene and understand how these variants affect nerve cells.

Another team, led by researcher Alex Hewitt, PhD, from the Menzies Institute for Medical Research at the University of Tasmania, received a AU$50,000 (about $38,730) research grant to investigate if a novel enzyme, engineered using the CRISPR/Cas9 genome editing technology, is able to correct a CLN2 gene variant — responsible for late infantile Batten disease — in a preclinical model of the disease.

This type of gene editing approach, which can perform tailor-made genetic modifications in an organism’s genome, has the potential to be a disease-modifying therapy for Batten.

Another project, led by Nadia Mitchell, PhD, at Lincoln University, in New Zealand, was awarded a AU$56,440 (about $43,720) research grant. Researchers in Mitchell’s lab have developed well-established sheep models of CLN5 and CLN6 Batten disease. Following positive results of a single administration of a combined gene therapy directed at the brain and eye at different stages of CLN5 disease in these animal models, the team is preparing to submit a new drug application to the U.S. Food and Drug Administration, with the goal of advancing into a clinical trial next year.

This project will test equivalent doses and delivery routes in sheep. The objective is to understand the changes that happen in the brain, eye, and spinal cord of affected sheep, and translate them to humans.

A research project led by Ronald Clarke, PhD, and Alvaro Garcia, PhD, from the University of Technology, in Sydney, received a AU$21,256 (about $16,465) research grant to study the effects of fatty molecules in the cell membrane surrounding the CLN3 protein. This protein is located within an intracellular membrane. It has been previously shown that certain molecules — similar in structure and chemical composition to cholesterol — exert a protective effect in animal models of CLN3 disease through the cellular membrane.

As such, researchers hypothesize that these molecules exert their effect through the membrane: either the membrane that directly surrounds the CLN3 protein or a membrane located in another place of the cell. The team wants to test its hypothesis and discover which membrane properties need to be changed to ease disease symptoms in mouse models of CLN3 disease.