GeNeuro presented groundbreaking findings on its GNK-301, a potential precision medicine strategy for ALS, at the 35th International Symposium on ALS/MND in Montreal. The research highlights the potential of GNK-301, a humanized monoclonal antibody targeting HERV-K ENV, a neurotoxic protein found in the cerebrospinal fluid of ALS patients, to transform ALS treatment.
Targeting HERV-K ENV in ALS
Studies have demonstrated that HERV-K ENV contributes to neuronal cell death and blood-brain barrier (BBB) dysfunction, both key features of ALS pathology. GNK-301 can detect HERV-K ENV in cerebrospinal fluid samples and neutralize its harmful effects.
In preclinical studies, GNK-301 abolished the neurotoxicity of ALS cerebrospinal fluid in iPSC-derived neuron cultures and neuronal death in mice injected with HERV-K ENV. The presence of HERV-K ENV in the brain also reproduced the BBB dysfunction observed in ALS brains, which was prevented by GNK-301. When labeled GNK-301 was injected intravenously in mice, it accumulated in brain regions where HERV-K ENV protein was present.
Clinical Implications and Future Directions
"We are excited to share these promising findings and congratulate the NIH/NINDS, ERBC and the University of Oxford for this exciting new data that opens a path towards a novel precision medicine approach in the treatment of sporadic ALS," said Hervé Perron, CSO of GeNeuro.
Individuals with ALS who produce endogenous autoantibodies against HERV-K ENV tend to live longer, supporting the therapeutic potential of GNK-301. GNK-301 has a greater affinity and neutralizing effect compared to autoantibodies. The effect of HERV-K ENV on the BBB facilitates the transport of the antibody into brain tissue after intravenous administration.
GeNeuro is planning for the required medical-grade production of GNK-301 to provide the antibody for clinical studies in ALS patients who test positive for HERV-K ENV using GeNeuro’s dedicated immunoassay. This represents the first integrated strategy for precision medicine in sporadic ALS.
