Meeting the Challenge of CTE

Today, January 30, is the second annual CTE Awareness Day. CTE, or chronic traumatic encephalopathy, is a progressive disease caused by repetitive brain trauma. It is most often found in athletes involved in contact sports and members of the military. CTE’s symptoms can include aggression, depression, impaired judgment, impulse control problems, memory loss, suicidal thoughts, and dementia.

The Alzheimer’s Drug Discovery Foundation (ADDF) supports research to prevent and treat many causes of dementia, including CTE. CTE is classified as a tauopathy, meaning people with the disease have neurofibrillary tangles containing tau in their brains. Other tauopathies include progressive supranuclear palsy (PSP), primary age-related tauopathy, and some forms of frontotemporal dementia (FTD). Tau tangles are also a defining component of Alzheimer’s disease.

The ADDF's Efforts

To treat CTE, we first need to identify patients who have it. Right now, CTE can only be conclusively diagnosed in patients at autopsy. Diagnosing CTE based on number of traumatic brain injuries or symptoms is challenging. We don’t yet know how many brain traumas put patients at risk for CTE. Symptoms can also take years or even decades after the last brain trauma to appear.

Our best option in the near future is neuroimaging of tau tangles. In 2016, a group of neuropathologists convened by the NIH published diagnostic criteria that differentiated CTE from other tau-related diseases based on the location of tau in the brain. This consensus meant that if researchers could image tau in living patients, they could diagnose CTE based on its location.

With funding from the ADDF, two researchers are now developing PET scans for tau imaging. At Mount Sinai, Dr. Sam Gandy is conducting PET scans using both a tau tracer and an FDA-approved beta-amyloid tracer. His goal is to differentiate patients with CTE. Dr. Neil Vasdev at the University of Toronto and Harvard Medical School is comparing different tau tracers to see what types of tau in what brain regions are visible on PET imaging scans. Both are attempting to “validate” tau PET tracers, which involves testing them on patients and comparing the results to other diagnostic tools. The goal is to develop a PET scan that is sensitive enough to detect various types of tau deposits (and only tau) in the regions of the brain relevant to CTE or other diseases.

While validated tools for detecting tau tangles are still in development, treatments to target the abnormal deposition of tau are already being tested. Asceneuron’s ASN120290 is in a phase 1 trial and will be tested in patients with progressive supranuclear palsy in phase 2. Yuma Therapeutics is preparing to begin trials with its drug YT-83. And Dr. Travis Dunckley at Arizona State University is nearing the clinic with a Dyrk1a inhibitor. All of these programs received funding from the ADDF. And our 2017 Clinical Trials Report lists more drugs targeting tau, including six monoclonal antibodies.

Most of these drugs are being tested in patients with dementias such as PSP and Alzheimer’s, but they have potential for CTE patients. As PET tau imaging in CTE advances, we are becoming better able to identify and enroll CTE patients in clinical trials. CTE research is relatively new, but it is advancing rapidly—and the ADDF is doing all we can to support its progress.