” Det finns ouppfyllda behov av nya behandling av psykos”

Publicerad 16 oktober, 2020

Sophie Erhardt, (professor på institutionen för fysiologi och farmakologi på Karolinska Institutet) har tillsammans med Lilly Schwieler, senior forskare på samma institution som mål att upptäcka en läkemedelskandidat som kommer att minska överaktivitet i dopaminerga projektioner hos patienter med neuroinflammatorisk inducerad psykos.

Sophies projekt får stöd från KI Innovations START-program och vi ställde henne några frågor om hennes resa, hennes lärdomar hittills och hennes framtida planer för projektet.

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Provide a short summary of the project that you intend to create impact from.

Novel treatment of psychosis is a highly unmet clinical need. Emerging evidence implies immune activation as an underlying pathophysiological factor. Our aim is to discover a drug candidate that will decrease overactivity in dopaminergic projections in patients with neuroinflammatory-induced psychosis.

Our finding that brain kynurenic acid (KYNA) is increased in psychosis has inspired drug companies to develop kynurenine aminotransferase (KAT) II inhibitors, i.e. drugs known to inhibit the synthesis of KYNA under normal conditions. Groundbreaking studies from our laboratory have, however, identified another mechanism as responsible for the de novo production of KYNA during conditions of immune activation.

Together with the Drug Discovery and Development (DDD) platform at Science for Life Laboratory (SciLifeLab) in Stockholm/Uppsala, we have established high throughput screening (HTS) assays and screened for compounds inhibiting this enzyme. The HTS of the SciLifeLab 33k compound library is resulted in 2-4 series of compounds which have been verified as binders using surface plasmon resonance spectroscopy (SPR) and characterized for several in vitro ADME properties. Lead compounds have been identified and are analyzed with regard to their efficacy to reduce KYNA concentrations in human cells as well as in disease-relevant animal models utilizing the in vivo microdialysis technique. We will also investigate drug-induced effects on brain neurotransmission in these animal models.

This is a novel treatment regimen for Psychosis and Cognitive Impairments without targeting the dopamine system and thus having less risk for side effects.

If successful, this drug will target recently discovered causal disease mechanisms and significantly improve life quality for affected individuals and families.

Who is the future user of the treatment.

Individuals suffering from psychotic symptoms and/or cognitive deficits may benefit from this kind of treatment. Patient groups will include patients with schizophrenia and bipolar disorder but also all individuals suffering from immune-induced cognitive deficits, such as patients with HIV, Herpes encephalities, TBE, Covid-19.

What is the current status of your project from an impact creation point of view?

We are close to identifying a candidate drug with satisfying potency. With that in place we will be ready to file a patent and that will be soon.

What steps have you taken towards impact creation through commercialization?

I have had a chance to participate in numerous programs and courses provided by KI Innovations that have help me on my journey.The M4R program at KI Innovations in 2019 facilitated discussions with stakeholders and biotech companies. The course ”Get started”  during spring 2020 gave me tool to take this project towards impact creation.

What are your key learnings so far in relation to impact creation and commercialization?

To understand the customer. Who will benefit from using this drug? What kind of symptoms will our drug treat? Who is our target group and what is the problems they face? What other stakeholders actively target our target group with respect to the problem intended?

Also to understand the prevalence and incidence of each disorder our drug might target. And one of the key issues is that the timing of filing a patent is very important.