Research program update September 2022

Progress with assays and biomarkers

SPG7 research

Gautam Wali

The current SPG7 research project, funded by the SP Foundation (US), has now been completed by Dr Wali and his team in Prof Carolyn Sue’s lab at the Kolling Institute, Sydney University. Using induced pluripotent stem cell-neurons developed from tissue samples of people with SPG7, the team has established a suite of assays that identify disease-associated impairments in patient cells. 

The next step is to use these high-throughput assays to test and screen for drugs that correct the impairments and restore normal function in the SPG7 stem cell-neurons.

The major work of the quarter has been the completion of this project. They will now work on drafting a scientific paper for publication and seeking out funding opportunities for the next phase, drug discovery.

SPG4 biomarker

We are hopeful of Dr Wali being able to validate the blood biomarker compound as a measure of disease progression in SPG4. One of the issues in delaying going to clinical trial is the lack of a definitive marker of disease status over time. Given the slow rate of progression in SPG4, a phase 2 trial needs to be of at least 12 months duration. Over any given 12-month period in people with SPG4, normal disease progression would span a wide range, meaning some people would remain pretty much the same, some would have minor worsening of symptoms and others would experience significant worsening of symptoms in that timeframe.

The challenge in a clinical trial is to accurately gauge the difference over the 12 months, and then compare progression between the group that is being treated and the group receiving dummy medication. The process of obtaining suitable blood samples for this biomarker validation study is underway.

Developments in gene therapies

We are keenly watching developments in therapies for children with HSP. In the June update, there was an article on parallel drug and gene therapy development in SPG56 that is underway in Queensland, with the drug development pathway being investigated at Griffith University and the gene therapy pathway proceeding at the University of Queensland.

In March in Toronto, Canada, a four-year-old boy with SPG50 underwent gene therapy, a procedure where a healthy copy of the AP4M1 gene was injected into the boy’s spinal fluid. The procedure proved safe, with effectiveness to be assessed over the coming months.

Two families in the US, each with a child who has a sporadic, complicated form of SPG4, have teamed up to initiate a gene therapy program in which the treatments are currently being tested on SPG4-affected mice.

Also in the US, we have reported previously on the development of a candidate drug for motor neuron disease (MND) at Northwestern University in Chicago that also holds potential for treating HSP. Recently it has been reported that studies have found that the compound, known as NU-9, lengthened the axons of diseased neurons in mice with motor neuron disease. The treatment was found to be more effective than existing drugs for the disease, but with enhanced effect when given in combination with the existing drugs. Animal studies are continuing with the prospect of clinical trials early next year.

You can read articles on these developments in the Foundation News section on the website homepage.

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