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HD Immune: Developing a novel therapy for Huntington’s disease

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HD Immune: Developing a novel therapy for Huntington’s disease

HD Immune is developing a novel monoclonal antibody therapy for Huntington’s disease patients, aiming to interfere with disease progression and delay symptom development.

Huntington’s disease is a rare neurological condition with no cure. The condition is caused by a genetic mutation that affects a specific gene called huntingtin (HTT) and is fatal.

Symptoms of Huntington’s disease include involuntary movement, cognitive decline, speech and breathing difficulties, mood and behavioural changes and more. These symptoms are dramatic, and there are no treatments that have been developed that can help alleviate them. 

Now, HD Immune is working to develop a new antibody-drug which could potentially provide an innovative treatment option for patients to help improve symptoms of the condition.

HD Immune is headed by molecular biologist Dr Stefan Bartl and virologist Dr Lionel Wightman. 

Bartl studied at the University of Vienna, going on to work in biotech focusing on neuroscience and antibody development, and Wightman studied Applied Biology at Imperial College London, obtaining a PhD in Virology from Reading University and going on to work various positions including CEO, CFO and COO.

Bartl was responsible for the Huntington’s disease project of the Neurodegeneration Group at AFFiRiS AG, a clinical‑stage biotechnology company developing novel therapies for neurodegenerative diseases, where he was in charge of the development of a new therapeutic concept in Huntington’s disease. The concept targeted mutated HTT protein with monoclonal antibodies.

NR Times speaks to Bartl and Wightman about HD Immune’s recent and future research on its journey to seek out new treatments for this rare condition.

What is the current state of care for Huntington’s disease patients?

Bartl: So far, there’s no treatment available. It’s deadly and it’s not curable. There’s a lot of pain and a lot of bad processes going on with the patients who finally die. It’s also a social problem because of the families involved, the care of the patients is complicated and not so easy. 

In Huntington’s disease, the cause of the disease, or the driver of the disease, is absolutely well known because it’s a single gene location. So it’s also called a monogenic disorder. When there is a mutation, people get this disease. 

Our aim is that we want to get rid of this mutated protein in the patient. And this is, from our perspective, a more ecological approach. We want to develop this antibody therapy which binds to the protein specifically and the protein should be reduced in the body. 

This is very important as it delays the progress of the disease. We are aiming to reduce and to neutralise the pathological process. 

Wightman: You see, the plaques accumulating in brain disease are actually over the whole body, not just the brain, it is all the other organs of the immune system as well. So, our approach you could say is sometimes the antibodies cannot get into the brain stem, but this is a whole systemic body disease. 

We did see that reduction in the intensity of plaques. So there’s obviously something going on there and the blood brain barrier, which usually blocks everything, is not tight anymore. It’s looser. So there may be a chance that we’re seeing some positive effect around the brain area. Our main point is when you reduce your systemic toxicity, things like that liver can regenerate, which we’ve seen in the mouse model, and we’re hoping to repeat for humans.

What is the hope for this treatment?

Bartl: We choose a mouse model which expresses the full Huntington gene, a mouse model which recapitulates the disease in many respects. What is very characteristic for this disease is movement disorder where the movements cannot be controlled by the patients. 

It’s very important to choose this animal model as it shows movement disorders. These animals are not running normally, so we focused on these animals on this movement, we focus on the amount of pain and we focus on aggregates in the brain. These were three hallmarks of the disease. 

We could show in this animal treatment that we could reduce the mutated protein in different organs, not just the Central Nervous System. We could show that the movements of animals could be improved, compared to controlling antibody treatment animals. We could see that after this treatment, we could reduce the intensity of aggregates, it was statistically significant, and very close to significance we could also see a reduction of the number of aggregates. So, we could see a positive effect. 

This Huntington protein is expressed in the whole body of the patient, not just the CNS. The whole body and other organs and tissues are affected, and also the immune system. When you’re developing therapy focusing just on the central nervous system, you cannot treat the rest of the body but the rest of the body is also suffering and the patient gets problems.

With our approach, we reach the body. So it’s a systemic treatment. It is molecules in the body of the patient, which are able to bind to protein in many many different tissues, in the periphery, let’s say, but also the central nervous system. So we can target both the central nervous system and the rest of these issues.

With a mouse model, the antibodies cannot be applied to humans, so we have to develop a human antibody which can then be applied.

Wightman: The treatment will be a regular injection of antibodies to the muscle once a month. We treated the mice for three months. If you do a very crude experiment this would be like delaying the disease for 10 years. 

What are your plans now to move into human trials? 

Bartl: We are in the process of developing the human molecule. We have a co-operation with the University here in Vienna, which are absolute experts in this field. These experts will help to develop this human molecule and we will select a lead molecule at the end. We will have to show that this molecule is doing what we expect, with clear experiments where we can show certain activity in an organism and there will be a toxicity study. 

I would say 2026 is when the molecule which could be ready to go to the clinic. We have to raise money to bring this forward.

Wightman: We have four people working on this antibody in the laboratory, which is one of the top in the world and we’re also looking to do experiments for confirmation with the top Huntington laboratories from around the world. 

HD Immune will be looking to raise £2 million in Seed funding and later, £6 to £8 million for the first Phase I trial.

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