Woolsey Pharmaceuticals announced findings indicating that BRAVYL (oral fasudil) significantly reduces the spread of toxic TDP-43 pathology in patients with Amyotrophic Lateral Sclerosis (ALS). The data, presented at the 35th International Symposium on ALS/MND, suggest a potential disease-modifying effect of BRAVYL by targeting the exosome-mediated spread of TDP-43, a key pathological hallmark of ALS.
The study, conducted by Dr. Daniel Linseman's laboratory at the University of Denver, examined neuron-derived exosomes (NDEs) from six ALS patients before and after six months of treatment with BRAVYL at 180 mg/day. These NDEs were then applied to a mouse motor neuron model to assess TDP-43 aggregation and cytoplasmic redistribution, characteristic features of TDP-43 pathology in ALS.
Key Findings on TDP-43 Pathology
The research team isolated neuron-derived exosomes (NDEs) from the plasma of healthy controls and ALS patients. The ALS patient samples were taken both at baseline and after six months of BRAVYL treatment. The results demonstrated:
- NDEs from untreated ALS patients induced marked aggregation and redistribution of TDP-43 into the cytoplasm of motor neuron-like cells.
- In contrast, NDEs from the same patients after six months of BRAVYL treatment showed a significant reduction in TDP-43 aggregation (60%, p=0.0006) and cytoplasmic redistribution (61%, p<0.0001).
These findings suggest that BRAVYL may be exerting a beneficial effect on the spread of TDP-43 pathology in ALS by modulating the contents of neuronal exosomes.
Implications for ALS Treatment
"We have previously shown that 6-month treatment of ALS patients with BRAVYL reduces Neurofilament Light Chain (NfL)," said Sven Jacobson, CEO of Woolsey. "Now we have evidence that BRAVYL can reduce the spread of toxic TDP-43, a truly novel discovery. These findings highlight BRAVYL's potential to transform ALS treatment."
ALS is a devastating neurodegenerative disease with a mean survival time of only two to five years. The disease is characterized by the accumulation of misfolded TDP-43 protein in the cytoplasm of neurons, leading to neuronal dysfunction and death. Current treatments for ALS offer limited efficacy, highlighting the urgent need for novel therapeutic strategies that target the underlying disease mechanisms.
Ongoing Clinical Trials
Woolsey Pharmaceuticals has completed recruitment for the high-dose (300 mg/day) cohort of the REAL study, which was added following promising NfL biomarker and clinical findings, along with a favorable safety profile observed in patients treated with 180 mg/day of BRAVYL. The company anticipates results from this study in June 2025.
