Author: Rachael Hansford

Via Newswise, 12 November 2024: University of Wisconsin–Madison researchers targeting a group of hereditary neurodegenerative diseases have found success using a gene therapy treatment in an animal model. The approach, which uses CRISPR-Cas9 genome editing technology, offers a strategy that could one day treat motor neuron diseases in humans. Hereditary spastic paraplegia, or HSP, is a group of movement disorders that cause progressive weakness and stiffness in the legs of people with certain inherited genetic mutations.  

Studying disease processes in animal models is part of developing and testing any new treatments before they’re offered to humans. But scientists had historically struggled to replicate HSP’s symptoms and disease progression in animal models. 

That changed in 2022, when a group of UW–Madison scientists led by Anjon Audhya, a professor of biomolecular chemistry, used CRISPR-Cas9 technology to develop a rat model that carries a genetic mutation associated with HSP.  

The mutation is in the Trk-fused gene, which typically facilitates the transportation of proteins within nerve cells called neurons. When that function is disrupted in people — and rats — it leads to worsening symptoms of weakness and stiffness.  Audhya and his colleagues recently developed a strategy that protects rats that carry a genetic mutation causing HSP from developing symptoms. 

That approach relies on a genetically engineered virus that targets neurons and introduces a normal version of the Trk-fused gene (which doesn’t include disease-causing mutations) to compensate for the mutated one. The scientists injected this engineered virus into the brains of day-old rats.  

Those animals never got disease. So they were able to live for many, many additional weeks, never showing signs of disease. It’s a real demonstration that the gene therapy approach is highly effective in addressing disease symptomology – Anjon Audhya

Specifically, the gene therapy approach allowed the non-mutated gene to be expressed in neurons and better support the transportation of proteins, preventing disease. The group recently reported their findings in the journal Proceedings of the National Academy of Sciences.  

Additionally, the researchers made a fundamental discovery about HSP — it’s primarily a disorder of neurons, rather than other cells found in the brain. When the team tested a similar strategy on cells called astrocytes, those animals still developed disease. 

Audhya and his colleagues are already moving on to follow-up studies developing another animal model and targeting a different gene mutation, which is more prevalent in HSP patients. They’re also planning to inject therapeutics via the spinal cord, which is closer to how treatment in humans would occur.  

Because HSP is a rare disease, funding for these studies can be difficult to secure. Audhya notes the support his team has received from Blu Genes Foundation, The Lilly and Blair Foundation and CureSPG4 Foundation has been a crucial part of their progress toward a potential cure for HSP. 

“We ultimately hope our preclinical gene therapy efforts will lead to a new clinical trial in patients in the years to come,” he says. 

Tourettes Action have created a new e-learning module, Understanding Tourette syndrome for GPs.  This course has been created with the help of Dr Kate Szymankiewicz, a GP with an interest in Tourette syndrome and clinical experts from the Tourettes Action Board of Trustees.  

In this module, you will learn what Tourette syndrome is, co-occurring features and differences that accompany it, how it affects an individual and what can be done to help and understand. 

Course Length: The course will take between 30 to 45 minutes to complete.

The course has 20 lessons split into the following sections:

• What is Tourette syndrome – this section details what Tourette syndrome is, the prevalence of Tourette syndrome and misconceptions that surround it, along with a number of case studies.
• Symptoms of Tourette syndrome – this section details what the symptoms of Tourette syndrome are, what are motor and vocal tics, how these are defined into simple and complex categories, what are coprophenomena and what are repetition and hidden tics.
• Co-occurring symptoms – this section delves a little deeper and details the co-occurring features that can also accompany Tourette Syndrome and how these affect the individual. It also touches on the impact of TS and how Tourette syndrome can affect an individual from a physical and emotional level.
• Differential Diagnosis – this section covers other movement disorders and what you should look out for.
• Support and Specialist Input – this section details what support is available for people with Tourette syndrome, their families and friends and anyone supporting them and when as a GP you should refer on to paediatrics, neurology, CAMHS or CMHT.

Find the course online here.