New vectorized antibody treatment for ALS

Our program in ALS has the potential to significantly delay disease progression and preserve quality of life in the majority of people by targeting the hallmark of ALS: TDP-43 misfolding and aggregation.

What is amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (NMD) or Lou Gehrig disease is a rare neurodegenerative disease characterized by the rapid and progressive loss of motor neurons, leading to paralysis, and death due to the inability to breath. In 90-95% of ALS cases the cause is unknown and there is no cure. Scientific discoveries have revealed new ways to potentially treat neurodegeneration in ALS.

The role of TDP-43 in ALS

The TAR DNA-binding protein 43 (TDP-43) protein is normally present in the nuclei of cells where it is essential for cell health. In most people with ALS the TDP-43 protein is misfolded and builds up (aggregates) in the cytoplasm of motor neuron cells. This is problematic for two reasons. Firstly, it leaves too little functional TDP-43 in the nucleus. Secondly, the buildup in the cytoplasm is toxic. The combination of too little nuclear TDP-43 (loss of function) and toxic cytoplasmic aggregation (gain of toxicity) is thought to contribute to loss of motor neuron cells in ALS. A potential medicine should therefore remove aggregated cytoplasmic TDP-43 and at the same time increase TDP-43 levels in the nucleus.

Vectorized antibodies to treat neurodegeneration in ALS

We believe vectorized antibodies hold great promise for treating ALS. A vectorized antibody consists of two parts. The first is the transgene that carries the instructions for a cell to make the therapeutic antibody. The second part is the vector into which the transgene is packaged and delivered to brain cells. We use AAV vectors, the same delivery method used for gene therapies.

What is VTx-002

VTx-002 has the potential to significantly delay disease progression and preserve quality of life in the majority of people with ALS. VTx-002 is a vectorized antibody that consists of a vector and the transgene that carries the instructions for a cell to make the therapeutic antibody. The antibody selectively binds toxic TDP-43 aggregates and clears them from the cytoplasm. Subsequently, it restores the essential function of TDP-43 in the nucleus. VTx-002 is currently in the pre-clinical testing phase.