Progressive Supranuclear Palsy (PSP) is a rare (but not ultra-rare), fatal degenerative neurological disorder; it affects about 20,000 people in the United States and has a similar occurrence rate in other parts of the world where the frequency has been examined well. PSP results in progressive impairment of balance and walking; impaired eye movement, abnormal muscle tone, speech difficulties, and problems related to swallowing and eating. Patients also frequently experience personality changes and cognitive impairment. Symptoms typically begin after age 60 but can begin earlier. The cause of PSP is unknown, and the disease is often initially misdiagnosed as Parkinson’s disease. No disease-modifying treatments have been approved for it yet.
In PSP, a set of research studies has provided evidence for a genetic and physiological role of tauC3 in PSP. First, a gene variant, rs1768208, located on chromosome 3, has been identified in two genome-wide association studies. In these studies, it was present in a high proportion of patients with PSP as compared to unaffected individuals. Importantly, the second, larger, study built on the first one by including a separate group of patients from a different part of the world.
Second, biological consequences of the gene variant were identified in a set of research studies. In these studies, it was found to be related to increased production of tauC3, and in the second study, the mechanism of the increased production was clarified. Thus, taken together, the data suggest that TBL-100 could be beneficial for PSP.