Interview: Hope for those with degenerative brain disease PSP
28 Mar 2023
Phase 1License out/inOrphan DrugPhase 2
Like Alzheimer’s, PSP is caused by a build-up of tau in the brain damaging cells. Build-up of the protein is caused by increased activity of enzymes that act on it called tau kinases, which causes the tau protein to misfold and clump, forming neurofibrillary tangles.
The disease is finally attracting some attention after successful results from trials.
A collaboration was formed in February this year (2023) which saw Swiss clinical stage biotechnology company Asceneuron sign a licensing agreement which gave Ferrer exclusive worldwide rights to develop and commercialize Asceneueron’s ASN90 drug.
Keen to find out more, OSP interviewed Dirk Beher, CEO and co-founder of Asceneuron alongside Oscar Perez, chief marketing officer, pricing and market access and business development officer for Ferrer.
OSP: There seems to have been an increase in awareness of PSP, has this made people recognise the symptoms sooner?
Óscar Pérez Albet: I was pleased to be invited to this interview because I believe we need to keep highlighting, investigating, and developing a treatment for PSP. PSP is a degenerative brain disease, and the cause is still unknown.
Tau eventually starts to deposit in certain areas of the brain, and because of that the brain cells/neurons are damaged and affected, and this is when the symptomatology starts – the most notorious and initial symptomatology and probably the most important and significant.
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There’s a whole bunch of different symptoms, a variety of them, but those that are much more specific to this condition are loss of balance, the slowing of movement, difficulty in moving the eyes, and it can even in impair the cognitive function of our brain. What's important to understand is that people new to this condition trying to understand it is that tau protein exists in the body.
In normal conditions it has a crucial role, an architectural one as it plays a key role in stabilising the neural network in the brain crucial for our normal functioning and for our brain activity.
Dirk Beher: A particularly unusual characteristic of this disease is falling backwards as well as all the ones Oscar described so well.
To expand upon tau a bit more, it is a protein that's required for neurons to function and for the brain too. If you see it precipitating or depositing, something is clearly wrong. We now have a chance to develop drugs - and that’s our mandate – to prevent deposition of this protein. With our ASN90 molecule we have shown with laboratory experiments that we can prevent the precipitation, and that's our whole hypothesis. We don’t know the cause and we don’t know why it precipitates but what we do know is that we want to address it.
We're quite hopeful we have a treatment and the reason for that is because of what we have seen in Alzheimer's - seeing beta amyloid precipitating preventing that amyloid being efficacious.
OSP: Is this a treatment you’re trying to develop for the early stages of PSP, or can it be applied to patients whose disease has already progressed?
Dirk Beher: We begin when people already have symptoms, but we can start the disease biomarkers earlier and earlier, so they are more indicative. With PSP we are at the start, but for Alzheimer’s Disease we have a huge data set already available. We are now trying to move back to catch patients earlier, but we dependent on patients showing PSP symptoms for the trials so we can categorise them as PSP patients - and not as having other rare diseases.
Óscar Pérez Albet: The point is that this is a devastating condition, and as with many other rare diseases and rare conditions, it is easy to find under-served patients because of the lack of research, the lack of apps currently available and lack of existing treatments. This is a particular issue with syndromic symptoms, and we refer to a syndrome when we refer to specific diseases with a collection of symptoms not specific to a certain disease – there are a few like that.
Because of the lack of resources in terms of generating awareness of these diseases directly translating into the proper diagnosis, it can cause a certain misunderstanding unfortunately delaying the diagnosis. We need to do much more and part of our conjoined strategy is to keep working with patient associations and many of the disciplines in the medical setting and we need to learn to become suspicious of symptoms earlier.
OSP: Is there any reason why it targets people or is it just completely random?
Dirk Beher: It's non-discriminatory and can happen in men or women, and there's no racial, geographical or any other factors whatsoever. As with all new generator diseases, the main risk factor is age.
That's why the onset usually comes between 60 or 70 years of age. Why this is we don't know, but it it's very common across all the natural diseases. Just to make it very clear, we haven't seen any bias towards anything.
Óscar Pérez Albet: There are specific symptoms, and this is probably what is much more important, for example backwards falls because patients become unable to move their vertical axis. Once we understand that there is no kind of bias, and another important symptom to note is general muscular stiffness. As long as we promote awareness, we are going to increase diagnosis and find a meaningful treatment which is the combination we are all striving for.
A meaningful treatment would be the success that we are all waiting for.
OSP: How long do you think a patient could be suffering from PSP without realising they have it?
Dirk Beher: It's difficult. We started this project 2013 and this was completely unknown, but now I think people are getting more educated and I think that is because the companies that have run trials are certainly more aware but there are sub-types of PSP also.
Óscar Pérez Albet: We know that is that is a rare disease, but I would say beyond prevalence, that there is not as much data available and the kind of questions that you are raising are proper ones.
OSP: We have had trials that have been done and the discovery of your treatment. Do you know the plans, where are we going next with this?
Dirk Beher: I can speak about the future and exactly how it is going look. We have developed this in our company which we started in 2013. It's been a long time with a small team of highly experienced experts. And we looked time and time again at the disease and developing a tau drug, and we know we can find tau pathology.
When you look at Alzheimer's, I mentioned earlier that where you find beta amyloid, you find tau, you even find other pathologies. That's a very complex situation so when we carried out the first trial of the drug, we considered a disease where only tau is the driver and ended up with PSP. I don't want to go into too much detail because it gets very complicated. However, what has been done with the molecule we found is that we have been able to run three trials in healthy volunteers.
The typical development is the drug gets into the body but not the plasma, it gets into the blood stream and what's exciting is that we have shown with an imaging technique is that the drug goes into the living human brain and really binds to the target.
The one that has got enzymes and that was the most important data set generated, and the next step with all that data and if it's tolerated it will go to patients.
Óscar Pérez Albet: We plan to start a phase two of our clinical development plan and that will be followed by phase three. This is the traditional pathway, and we will demonstrate what potential an asset like the SN90 molecule has, especially based on efficacy and safety. We also need to look at the profile of the patient and their many different needs - not only the pharmacological ones and we need to start having early conversations with regulators.
OSP: What other therapies have been proven to be helpful before?
Dirk Beher: I think trying to moderate the symptoms but that depends on the patients. You can use some of the dopaminergic drugs that may provide some benefit for a certain period of time, but I think it is fair to say there is no treatment that can really change the disease, it is mainly to ease the patient’s life.
It was important for us to find a partner who can take this on to develop it further because we are a small company. I think we have found our forever partner here because Ferrer is committed to patients, they also have rare disease experience, and this was very comforting for us and you can see the excitement here when Oscar's speaks about moving this into patients knowing we will be making a difference.
Oscar Perez Albet: It's so important to raise the voice of the patients and to spread the word to generate awareness.
The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) granted orphan drug designations to ASN90 for the treatment of PSP. The OGA inhibitorOGA inhibitor was evaluated in three clinical studies including a double-blind, placebo-controlled, randomised phase 1 trial and human positron emission tomography (PET) CNS target engagement study.
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