Announcing the 2026 In Vivo Target Validation Projects
July 21, 2026 Michael DeChellis-Marks
Target ALS is proud to announce the newest projects selected through our In Vivo Target Validation Program, an initiative designed to accelerate promising ALS therapeutics toward clinical development. This cycle, we received 47 proposals and selected three for funding. The program is conducted in partnership with the contract research organization Biospective. It helps researchers test whether experimental therapies can engage their intended targets and modify disease biology in ALS mouse models, a critical step before a drug is able to move into clinical trials.
Each project brings a distinct approach to a shared goal: bringing effective treatments closer to reality.
Validation of PARP1 as a therapeutic target for ALS
Bhavya Voleti, Eikon Therapeutics (Millbrae, California, United States)
Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease with multiple genetic and non-genetic drivers of disease. In more than 97% of ALS patients, the disease is characterized by TDP-43 cytoplasmic mislocalization and an array of diverse mechanisms underlying ALS. Contemporary research has implicated poly(ADP-ribose) polymerase 1 (PARP1) hyperactivation in ALS pathobiology. PARP1 is a nuclear enzyme critical for DNA damage response, chromatin regulation, and metabolic homeostasis. Increased activity of PARP1 protein has been associated with multiple disease mechanisms of ALS, including increased DNA damage and cellular stress leading to motor neuron death. This study aims to evaluate whether inhibition of PARP1 may delay or prevent disease onset in a model of ALS.
Preclinical testing of a novel vectorized anti-TDP-43 intrabody therapy designed to broadly target neuropathology of ALS
Damien Nevoltris, AC Immune SA (Lausanne, Switzerland)
AC Immune has developed a viral therapy that enables neurons to produce intrabodies, engineered antibodies designed to function inside cells and selectively target harmful forms of TDP-43. Their approach combines a next-generation central nervous system (CNS) delivery system, TDP-43-specific intrabodies, and a platform that enhances their stability and expression within cells. This therapy is now being tested in a mouse model of ALS to evaluate its potential to modify the disease.
Evaluation of a novel TRPM2 inhibitor in a model of ALS
Mark Reed, University Health Network (University of Toronto, Toronto, Canada)
The TRPM2 protein plays a key role in activating inflammatory pathways. Dr. Mark Reed and his team at University Health Network have developed a TRPM2 inhibitor for diseases driven by brain inflammation, such as ALS and other neurodegenerative conditions. The team aims to test how small-molecule drugs that selectively block TRPM2 reduce harmful inflammation while preserving normal cellular function. Using advanced medicinal chemistry and biology, they have identified potent drug candidates that can reach the brain and will be further evaluated in disease models to assess their potential to slow disease progression.
Together, these projects highlight the breadth of approaches researchers are using to better understand ALS, spanning DNA damage response, viral therapy, and neuroinflammation. We look forward to sharing updates as this work progresses.
