Drug that reduces iron levels in affected brain regions has a possible disease-modifying effect in people with multiple system atrophy

HONOLULU, Oct. 5, 2025 /PRNewswire/ -- An orally administered drug to redistribute excess iron and lower cellular oxidative stress was found to slow disease progression of multiple system atrophy (MSA), according to a study released at the International Congress of Parkinson's Disease and Movement Disorders® in Honolulu, Hawaii, USA. 

MSA is a rapidly progressive disease that affects multiple body systems and is linked to the accumulation of alpha-synuclein in the brain. There is no cure or approved treatment for MSA, which underscores the significance of investigational therapies such as ATH434. ATH434 is designed to reduce excess iron and oxidative stress, which have been found to contribute to alpha-synuclein aggregation. By targeting these underlying mechanisms, ATH434 has promising potential as a disease-modifying treatment for MSA. 

"These study results are novel and exciting developments in the battle against a relentlessly progressive neurodegenerative disorder," said Peter LeWitt M.D., M.Med.Sc., Professor of Neurology and Pharmacology at Wayne State University School of Medicine and Sastry Foundation Endowed Chair in Parkinson Disease Research. "The reported efficacy after one year of treatment with compound ATH434 signals a new era for the disease modification of multiple system atrophy (MSA). 

In this randomized double-blind phase II trial by Stamler et al., participants with probable or clinically established MSA were given either 50 mg or 75 mg of ATH434 for 52 weeks. Compared to placebo, the 50 mg and 75 mg groups saw a representative disease slowing of 48% and 30%, respectively. Additionally, there was reduced iron in affected brain regions like the substantia nigra, putamen, and globus pallidus. There were no serious adverse events related to ATH434. 

"The range of reported positive findings helps to confirm a biologically plausible mechanism for ATH434; namely, that its alteration of brain iron metabolism results in decreased iron accumulation in MSA-affected brain regions," LeWitt said. "On this basis, ATH434 is suspected to lessen the pathological accumulation of alpha-synuclein, a key protein integral to the progression of MSA. While the reported study results suggest a clinically meaningful outcome, the full picture of ATH434 as a promising treatment for MSA awaits the full presentation of study results in a peer-reviewed publication. Nevertheless, demonstration of slowed worsening using standard MSA clinical ratings and compelling evidence for the drug's target engagement is very encouraging news for the worldwide community of persons suffering from this incurable disease."

The full text of the abstract is available at mdsabstracts.org.

A bout the 2025 MDS International Congress of Parkinson's Disease and Movement Disorders ^® : 
The MDS International Congress is the premier annual event to advance the clinical and scientific discipline of Movement Disorders, including Parkinson's disease. Convening thousands of leading clinicians, scientists and other health professionals from around the globe, the International Congress will introduce more than 1,800 scientific abstracts and provide a forum for education and collaboration on latest research and treatment findings. 

About the International Parkinson and Movement Disorder Society: 
The International Parkinson and Movement Disorder Society^® (MDS), an international society of more than 12,000 clinicians, scientists, and other healthcare professionals, is dedicated to improving patient care through education and research. For more information about MDS, visit www.movementdisorders.org. 

SOURCE International Parkinson and Movement Disorder Society