Development of a novel antibody therapy
for Huntington’s disease patients

 

Our mission

Huntington's Disease (HD) is a rare neurological disease with a fatal outcome that cannot be cured - to date no drug has been developed that can ameliorate the symptoms. Because of this urgent unmet medical need, HD Immune’s aim is to develop a monoclonal antibody, which can interfere with the disease progression, delaying further clinical symptom development.

HD Immune intends to use our proprietary knowledge for the development of a new antibody-drug which is potentially a first-in-class therapeutic intervention for this disease.

 

For more information about Huntington's disease please use the following links 1

 

 

About Huntington's disease (HD)

Huntington's disease (HD), also known as Huntington's chorea, is a debilitating neurodegenerative disorder that affects the brain's nerve cells. 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 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.

 

For more information about Huntington's disease please use the following links 1

 

 

HD Immune's approach

In Huntington's disease, the accumulation of a toxic protein called mutant huntingtin (mtHTT) is a key pathological feature. Due to a genetic mutation, the huntingtin protein gene contains an expanded CAG trinucleotide repeat, resulting in abnormal folding and aggregation. These aggregated proteins form clumps within neurons, impairing their function and ultimately leading to cell death. The accumulation of mutant huntingtin disrupts various cellular processes, including protein degradation, energy metabolism, and neurotransmitter signalling.

 

HD Immune’s approach is to interfere with extracellular and accesible 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.

 

For more information about antibodies and antibody therapies please use the following link 2

 

 

HD Immune development

HD Immune proprietary approached is based on published validated results 3 & 4 , the objective of the HD Immune program is to optimize the monoclonal antibody for use in human clinical trials.

This strategy is anticipated to lower mtHTT, and provide a new, disease modifying modality as alternative to current CNS targeting strategies which are under exploration.

 

  • Our immunotherapy targets the pathological HTT protein directly
  • Monoclonal Antibodies are well characterized medications with years of experiences in terms of development, production and safety
  • Treatment of patients is not expected to create negative side effects or toxic reactions
  • Similar antibody approaches are being developed for other neurodegenerative diseases like Alzheimer's disease (Lecanemab), which for the first time has demonstrated a clinical benefit for the patient 5 

 

 

 

HD Immune team and network

Stefan Bartl, PhD

Molecular Biologist 

Stefan studied Molecularbiology at the University of Vienna and moved early in his scientific career to the Biotech Industrie focusing on Neuroscience and antibody development. As Group leader of the Neurodegeneration Group at AFFiRiS AG he was responsible for the Huntington’s disease project and he was in charge for the development of a new therapeutic concept in Huntington’s disease targeting mutated HTT protein with monoclonal antibodies.

 

 

Lionel Wightman, PhD

Virologist

Lionel studied Applied Biology at Imperial College (London) and then obtained a PhD in Virology from Reading University as a Wellcome Trust Prize PhD student. Lionel has worked in different companies in various positions such as CEO, CFO and COO.

 

 

 

International cooperations

UCL, Orlando, FL, USA

Univ Laval, Quebec, CAN

UBC, Vancouver, CAN

 

 

References

1) https://www.ninds.nih.gov/health-information/disorders/huntingtons-disease

    https://www.hda.org.uk/

    https://www.fda.gov/search?s=Huntington%27s+disease

2) https://search.nih.gov/search?affiliate=nih&query=Antibody+development

3) Bartl S., Queslati  A., Southwell  A., Siddu A., Parth M., Maxan D.L., A., Salhat N., Burkert M., Mairhofer A., Friedrich T., Pankevych H., Balazs K., Staffler G., Hayden M., Cicchetti F. and  Smrzka OW.; The use of monoclonal antibodies to target extracellular mutant huntingtin: Implications for the treatment of Huntington's disease. Neurobiol Dis. 2020 May 11:104943. doi: 10.1016/j.nbd.2020.104943

https://pubmed.ncbi.nlm.nih.gov/32407769/

4) Bartl S., Xie Y., Potluri N., Kesineni R., Hencak K., Cengio L.D, Balazs K., Oueslati A., Parth M., Salhat N., Siddu A., Smrzka O., Cicchetti F., Straffler G., Hayden M.R. and Southwell A.L.; Reducing central and peripheral huntingtin by immunotherapy delays disease progression in a mouse model of Huntington disease; 2024, in press

https://doi.org/10.1016/j.nbd.2023.106376

5) https://search.nih.gov/search?affiliate=nih&query=Alzheimer%27s+disease+antibody+treatent&commit=Search

 

 

Our Partners

 

The HD Immune office is incubated at CEBINA (Central European Biotech Incubator and Accelerator) – a high-tech business incubator located at the Vienna Biocenter. The HD Immune Lab is incubated at the Institute of Molecular Biotechnology at the BOKU (University of natural Resources and Life science) in Vienna.

HD Immune received a pre-seed founding by the Austrian Federal Development and Financing Bank AWS and a founding from the Comet24 program sponsert by ACIB (Austrian Center for Industrial Biotechnology).