AC immune awarded grants supporting TDP-43 detection
Research grants are funded by the MJFF and Target ALS
AC Immune has been awarded two research grants to identify the presence of TDP-43, a protein that plays a key role in neurodegeneration underlying Parkinson’s disease and other neurological diseases.
The grants were awarded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF) and Target ALS.
“It is an honor to have the support of MJFF and Target ALS, two leading international organizations that recognize the pressing need for diagnostics to detect [disease-causing] TDP-43,” Andrea Pfeifer, AC Immune’s CEO, said in a press release. “There is currently no single test to confirm the presence of [TDP-43-related damage], and diagnosis is complicated by overlapping motor and clinical symptoms.”
“We firmly believe that a sensitive and accurate diagnostic will represent a breakthrough for the field and will accelerate clinical development of therapeutic candidates against this novel target,” Pfeifer added.
Parkinson’s disease is characterized by the loss of dopamine-producing nerve cells in certain brain regions. Dopamine is a chemical messenger that allows nerve cells to communicate, supporting many body functions, including movement.
Such nerve cell loss is thought to be caused by the accumulation of toxic clumps of the misfolded alpha-synuclein protein.
Like alpha-synuclein, misfolded TDP-43 also forms toxic clumps that have been implicated in several neurogenerative conditions. While these toxic aggregates are a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), they are thought to partly contribute to nerve cell death in Parkinson’s and Alzheimer’s disease.
Toxic TDP-43 buildup can occur in the brain before symptoms emerge, making a noninvasive test to detect TDP-43 in the brain important for an early and accurate diagnosis.
PET tracer program
The MJFF grant will support AC Immune’s TDP-43 positron emission tomography (PET) tracer program, a noninvasive imaging test with the potential to be the first to detect and monitor the progression of TDP-43-related diseases.
So far, the company’s TDP-43-PET tracers have demonstrated their ability to selectively target disease-causing TDP-43 in brain tissue. A potential candidate for future clinical trials is expected to be announced in upcoming months, according to the company.
The MJFF previously awarded AC Immune a grant to develop a PET tracer to detect alpha-synuclein aggregates to support early Parkinson’s diagnosis.
“Brain imaging agents uncovering aggregated [disease-causing] protein hold great promise to enable earlier and more accurate diagnosis of [neurodegenerative diseases], and we are pleased to be expanding our relationship with AC Immune to support its TDP-43 tracer program,” said Jamie Eberling, PhD, senior vice president of research resources at MJFF.
“AC Immune and its collaborators recently demonstrated their expertise in developing cutting-edge PET imaging agents by providing the first images of alpha-synuclein,” Eberling said, adding that “with this new grant, we hope to make similar progress in the development of a TDP-43-PET tracer.”
Detecting toxic TDP-43 in bodily fluids is another approach supporting early diagnosis and treatment for Parkinson’s, but also ALS, FTLD, and Alzheimer’s.
The Target ALS grant will support a collaboration between AC Immune, Kansas City University, Barrow Neurological Institute, and the International Center for Engineering and Biotechnology to advance the development of an antibody-based test to detect disease-causing forms of TDP-43 in bodily fluids.
“We are delighted to support the collaborative consortium in which AC Immune is participating,” said Manish Raisinghani, PhD, CEO of Target ALS.
“Our approach to encourage multi-disciplinary and cross-sectoral collaborations continues to accelerate ALS drug discovery,” Raisinghani said, adding that “the development of a TDP-43 specific biofluid-based diagnostic test has the potential to more rapidly enable confirmed early diagnosis.”
Pfeifer said that “given the [variable] and irreversible nature of neurodegeneration, our [personalized medicine] approach represents the most promising strategy to identify the right patients and treat them earlier.”