$1 Million challenge to develop a TDP43 biomarker

February 10, 2016 – WASHINGTON. The ALS Association, in partnership with ALS Finding a Cure announced a Grand Challenge to generate a biomarker to track TDP43 aggregation. The successful team(s) with the most developed plan will receive up to a $1 million investment.

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. For unknown reasons, veterans are twice as likely to develop ALS as the general population. There is no cure, and only one drug approved by the U.S. Food and Drug Administration (FDA) modestly extends survival.

Transactive response DNA-binding protein 43 (TDP43) is the primary protein aggregate (i.e. clumps of protein) found in the brain and spinal cord of people with ALS and in other neurodegenerative diseases such as frontotemporal dementia (FTD) and Alzheimer’s disease (AD), among others. Mutations in TDP43 are also a genetic cause of ALS. Normally, TDP43 is located in the nucleus of a cell. In the disease state, TDP43 aggregates accumulate in the cytoplasm (the area surrounding the nucleus). Abnormalities in TDP43 protein trafficking between the nucleus and cytoplasm have been implicated in the disease process. How TDP43 is linked to clinical disease and whether TDP43 cytoplasmic aggregates are toxic remains unclear.

The Grand Challenge will lay the groundwork to develop a positron emission tomography (PET) tracer specific for TDP43 aggregates to use as an ALS biomarker. Once developed, its use would be widespread from tracking TDP43 aggregation during the disease process to enhancing ALS clinical trials targeting TDP43.

There are two phases of the Challenge. In the first phase, grants of up to $1 million will be awarded to the team(s) with the most developed plan and the appropriate materials to develop the TDP43 tracer. The second phase, ensures that if the first phase is successful, funds will be provided to further develop the PET tracer towards the clinic.

Research teams that qualify for the Challenge, but are not limited to include the following: TDP, preclinical biology, radiochemistry, PET, discovery and medicinal chemistry groups. Interested groups can find full details of the Challenge here. Letters of intent and abstracts are due March 22, 2016. The Challenge Committee will issue requests for full proposals to the groups with the most promising proposals on April 11, 2016. Full proposals are due May 20, 2016, with winners announced in July 2016.

Source: The ALS Association