A novel RNA-based strategy for Spinal and Bulbar Muscular Atrophy 

July 23, 2025

Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s disease, is a rare, progressive neuromuscular disorder caused by a mutation in the AR gene, responsible for making a protein called androgen receptor. This condition primarily affects males and currently has no approved cure. 

As a 2025 Oxford-Harrington Rare Disease Scholar, Professor Carlo Rinaldi is developing an antisense oligonucleotide (ASO) therapy designed to target the cause of SBMA in two ways. In his interview, Professor Rinaldi shares what drives his work, the promise of this new approach, and how support from the Oxford-Harrington Rare Disease Centre (OHC) is helping move it closer to clinical application. 

What inspired you to focus your research on rare diseases? 

Professor Carlo Rinaldi: "My interest in rare diseases is driven by both scientific curiosity and the challenge of addressing unmet medical needs in this group of conditions. 

Scientifically, they offer an opportunity to investigate complex mechanisms of human biology from unique angles. Clinically, they allow developing a very direct and close-knit relationship with the patient community. I find nothing more exciting and fulfilling." 

Could you describe your awarded project and its potential impact on SBMA patients? 

Prof Rinaldi: "SBMA is a rare disease caused by an abnormally long repeating sequence of DNA in the AR gene. It’s an X-linked condition, which means that affected males, who only have one X-chromosome and a Y-chromosome, have only a single copy of this gene.  

The androgen receptor itself is present throughout the body, playing widespread roles from maintaining muscle mass to driving prostate cancer. 

My awarded project focuses on developing a type of therapeutic called an  ASO designed to simultaneously reduce the toxic, abnormal AR responsible for the disease, while promoting the expression of a more ‘benign’ naturally-occurring  version of the AR that lacks the domain where the expanded sequence of DNA resides. 

This project holds the potential to pave the way for novel therapeutic interventions that could be transitioned into clinical testing for a disease which currently lacks treatment." 

How does OHC support accelerate your research towards clinical application? 

Prof Rinaldi: "My program was launched in March 2025, so it is still in its early stages. However, the level of support and expert guidance provided by the Oxford-Harrington Centre has already enabled me to make remarkable progress.  

My Advisory Team is made up of experts who have successfully guided similar programmes through the development pipeline. This support is truly unparalleled and unlike anything I have experienced before; it goes all the way from strategic advice on optimising experimental approaches to securing additional funding for the research." 

What makes your approach a promising or novel strategy for treating SBMA? 

Prof Rinaldi: "This work is based on a discovery we made in the lab, which is that the naturally-occurring version of AR that lacks the repeated sequence of DNA, is able to  regulate AR’s activity that is impaired in SBMA, without affecting its other important functions. The novelty and promise of this approach lie in its capacity to preserve AR function, which is so essential in humans. If successful, this approach could offer opportunities for a nuanced, targeted intervention also for other diseases." 

What is the role of collaborations between academia, industry, and patient organisations in driving progress for SBMA research? 

Prof Rinaldi: "Partnering with both industry and the patient community will be absolutely essential to advance this project towards the clinic.  

One of the great privileges of my role as a clinician-scientist is maintaining close connections with the patient community. This ongoing engagement ensures that patients remain as informed and enthusiastic about this strategy as I am." 

Where do you hope to see your project in the next 2–5 years? 

Prof Rinaldi: "Looking ahead, I hope we will be able to test this approach in clinical trials. To this end, we are working hard in collaboration with the wider scientific community to ensure we have a well-characterised patient population, supported by appropriate clinical scales and reliable biomarkers.  

I strongly believe that, in order to accelerate progress and maximise the impact of our research, data sharing and collaboration are key, in rare disease research and beyond."