Woolsey Pharmaceuticals Reveals Breakthrough Findings Showing Spread of Toxic TDP-43 Pathology Greatly Reduced in BRAVYL® (oral fasudil) Treated ALS Patients

NEW YORK, Dec. 9, 2024 /PRNewswire/ -- Woolsey Pharmaceuticals, a clinical-stage pharmaceutical company developing BRAVYL (oral fasudil) for the treatment of Amyotrophic Lateral Sclerosis (ALS), announced that a poster by Dr. Daniel Linseman's laboratory at the University of Denver presented at the 35th International Symposium on ALS/MND held in Montreal, Canada on December 6^th showed that treatment with BRAVYL significantly reduced TDP-43 aggregation and cytoplasmic redistribution.

In ALS, TDP-43 pathology is understood to spread via extracellular vesicles, including neuronal exosomes, which are secreted by sick neurons and can be taken up by healthy ones. TDP-43 pathology is characterized by the translocation of TDP-43 from the nucleus, where it normally resides, to the cytoplasm and the formation of aggregates.

To assess whether BRAVYL affects this process, neuron-derived exosomes (NDEs) were isolated from the plasma of two healthy control subjects and from six ALS patients, at baseline and after six months of treatment with BRAVYL (180 mg/day). A mouse motor neuron model was used to assess TDP-43 pathology. NSC-34 cells were transfected with plasmid expressing wild-type human TDP-43 linked to td-tomato fluorescent protein. Transfected cells were then differentiated into motor neuron-like cells using retinoic acid. Differentiated cells were incubated with NDEs and examined by confocal microscopy to observe changes in td-tomato-TDP-43 subcellular localization and aggregation.

Key Findings Include:

• Cells treated with baseline NDEs from ALS patients showed marked aggregation and redistribution of TDP-43 into the cytoplasm, indicating that NDEs from ALS patients can confer TDP-43 pathology in this system.
• In contrast, when exposed to NDEs from the same patients following treatment for 6 months with BRAVYL, TDP-43 aggregation and cytoplasmic redistribution were significantly reduced by 60% (p=0.0006) and 61% (p<0.0001) respectively.

The findings indicate treatment with BRAVYL may be beneficially affecting the neuronal exosome-mediated spread of TDP-43 pathology in ALS. Further work is underway to identify the specific cargo responsible for this effect and the precise mechanism of action.

"We have previously shown that 6-month treatment of ALS patients with BRAVYL reduces Neurofilament Light Chain (NfL)," notes 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."

Woolsey recently announced it had completed recruitment of 31 ALS patients into the REAL study's high-dose (300 mg/day) cohort, which was added following promising NfL biomarker and clinical findings along with an excellent safety profile in patients treated at 180 mg/day. Results are expected in June 2025.

ABOUT ALS

ALS is a fatal neurodegenerative disease characterized by inevitable, and often rapid, decline in patients as the disorder advances (mean survival time is only two to five years). Accordingly, the ability to impede any worsening represents a meaningful advancement in efforts to enhance the prognosis and quality of life of individuals impacted by this devastating condition.

ABOUT WOOLSEY PHARMACEUTICALS

Woolsey Pharmaceuticals is expanding the boundaries of medical science. Our lead indication is Amyotrophic Lateral Sclerosis (ALS), a progressive and debilitating disease that ultimately is fatal. Our mission is to help usher in a new era of neurodegenerative disease treatment, saving and improving the lives of patients in need.

SOURCE Woolsey Pharmaceuticals, Inc.