PSP and CBS Patients
Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are rare neurodegenerative disorders associated with the accumulation of insoluble deposits of predominantly 4 microtubule binding domain repeat (4R) tau protein in specific brain regions, mainly in the absence of other pathogenic proteins including β-amyloid, which is found in Alzheimer’s disease.
Accordingly, PSP and CBS are classified as primary 4R tauopathies. There are currently no effective therapies for either disorder. From the onset of PSP and CBS, the lifespan of patients averages 7 years.
Progressive supranuclear palsy (PSP) is an uncommon brain disorder that affects movement, control of walking (gait) and balance, speech, swallowing, vision, mood and behavior, and thinking. The disease results from damage to nerve cells in the brain. The disorder’s long name indicates that the disease worsens (progressive) and causes weakness (palsy) by damaging certain parts of the brain above nerve cell clusters called nuclei (supranuclear). These nuclei particularly control eye movements. One of the classic signs of the disease is an inability to aim and move the eyes properly, which individuals may experience as blurring of vision.
Corticobasal syndrome (CBS) is a form of atypical parkinsonism (a parkinsonism-plus syndrome), which means that it shares some features with Parkinson’s disease such as stiffness (rigidity), tremor at rest, slowness of movement (bradykinesia) and postural instability (balance difficulties). It may also cause problems with memory and thinking. Corticobasal syndrome, however, is distinct from Parkinson’s disease in regards to other clinical features, its causes and its response to treatment.
Levels of Rho-kinase (ROCK) are elevated in both PSP and CBS and is thought to be involved in the accumulation of tau aggregates. It is hypothesized that fasudil, a ROCK inhibitor, will reduce levels of ROCK activity in the brains of PSP-RS and CBS patients, reducing 4R tau phosphorylation and aggregation, as well as inducing clearance of existing 4R tau aggregates that are the hallmark of the two diseases-
The ROCKIT-1 Study
(ROCK Inhibitor in Tauopathies – 1)
ROCKIT-1 is a phase 2a open-label study to assess preliminary safety, tolerability, and effect on neurodegeneration biomarkers of BRAVYL in patients with the 4-Repeat (4R) Tauopathies of Progressive Supranuclear Palsy-Richardson Syndrome (PSP-RS) or Corticobasal Syndrome (CBS). In addition, ROCKIT-1 will assess whether BRAVYL improves clinical features of the disease.
The study will enroll approximately 15 patients (10 PSP-RS, 5 CBS), all of whom will be treated with BRAVYL for 48 weeks.