Huntington’s disease is a debilitating neurodegenerative disorder that affects the brain’s nerve cells in the CNS as well organs and tissues in the human body. This hereditary condition is characterized by progressive and involuntary movements, cognitive decline, and emotional disturbances. Named after the physician who first described it, George Huntington, the disease typically manifests in adulthood, although it can appear earlier or later in life.

Huntington’s disease is caused by a genetic mutation that affects a specific gene called Huntingtin (HTT). The mutation involves the repetition of a DNA segment known as a CAG trinucleotide repeat. As this repeat expands beyond a certain threshold, it leads to the production of a toxic HTT protein that accumulates in the brain, causing damage to nerve cells and disrupting their normal functioning.

The symptoms of Huntington’s disease can vary widely among individuals and progress at different rates. The most prominent signs include uncontrolled jerking or writhing movements (chorea), impaired coordination, difficulties with speech and swallowing, and changes in mood, behavior, and cognition. As the disease advances, individuals may experience severe cognitive decline, including memory loss and impaired reasoning.

HD Immune is developing the first passive immunological approach for Huntington’s disease patients, with the aim to bind, neutralize and degrade extracellular pathologic mutated Huntingtin protein (mtHTT) using a humanized antibody specific to the structurally exposed Caspase 6 binding region of the HTT protein.

HD Immune’s approach is to interfere with the extracellular and antibody accessible mutated Huntingtin protein by a specific monoclonal antibody which has the potential to block/reduce intercellular mtHTT transmission and spreading of HD pathology. This reduction is expected to modify disease progression in the brain and periphery in HD patients.

HD Immune proprietary approach is based on published validated in vitro and in vivo POC results. The objective of the HD Immune program is to develop and optimize humanized monoclonal antibodies for use in human clinical trials. HD Immune has demonstrated that a long-term administration of a murine mAB C6-17 could delay disease progression in HD animal models expressing the full-length human mutant Huntingtin gene, supporting the hypothesis that targeting extracellular mtHTT can slow down the prion-like infectious process. The humanized lead candidate huC6-17 shows identical biological activities compared to the POC mAB C6-17 and was further optimized in terms of AB expression, AB structure and AB folding. This strategy is anticipated to lower systemically mtHTT and provide a new, disease modifying modality as alternative to current CNS targeting strategies which are under exploration.