List of questions

In what way can 5-HT influence the integrity of the blood brain barrier?

i.v. administration of 5-HT results in an increased permeability of the BBB

What is the current view in the scientific community on astrocytes involvment in pathologies in the CNS?

Some authors claim that the role of astrocytes in different CNS disorders are of central importance.

What CNS targets should we address with our protein based drugs, and what novel transporter receptors can we use for this?

Affibody AB is a protein drug development company based on a molecular platform of very small proteins (Affibody® molecules) , 6.5 – 12 kDa, that can be engineered to bind specifically and with high affinity to protein targets. A number of therapeutic leads specific for cancer receptors or inflammatory mediators are available for collaboration, and novel binders targeting new target proteins can be isolated from existing Affibody® libraries.
We are interested in exploring opportunities to use our Affibody® molecules in CNS pharmacology, especially in terms of BBB penetration / transport. Specifically, we would like to discuss suitable novel target proteins for enhanced BBB transport, as well as relevant protein targets for therapeutic intervention in CNS diseases.

How can we identify which CSF and/or plasma biomarkers to use to follow disease progression and disease-modifying drug treatment efficacy in Parkinsons disease? What animal models can be used to follow disease-modifying drug treatment efficacy in Parkinson?s disease?

BioArctic's mission is to develop effective treatments for neurodegenerative diseases caused by miss folded proteins such as Alzheimer’s and Parkinson’s disease. Our technology is used to isolate a variety of proteins implicated in CNS disorders, study their aggregation properties, prepare, stabilize aggregated species and develop protofibril specific monoclonal antibodies. A key challenge in working with neurodegenerative diseases is to identify and measure biomarkers relevant to disease in CSF and plasma. This is important both in following progression of disease and for the establishment of drug treatment efficacy in the clinic. Another major challenge is to establish a relevant animal model to follow efficacy of drug treatment and ultimately to be used in translation between animal and humans with the aim to predict the dose to man and optimal clinical study design.

Is there a theoretic rationale for why alpha 7 nicotinic agonists will be disease modifying in future treatment of Alzheimer´s disease?

Several alpha 7 agonists are in development, the most prominent is EVP-6124 - currently in phase 3 for AD. Very successful EVP-6124 phase 2 data for AD raised speculation about disease-modification.

To what extent and how are neuropeptides studied in research on CNS disorders? When do you use tissue samples?

It is problematic to find relevant biomarkers for neurodegenerative disorders. Biomarkers are often quickly degrading, low abundant and easily masked by degradation products from higher abundant proteins. Is this a concern? If heat stabilization would be a solution to this, would that be of interest?

Today there are no neuron protective agents in clinic. What kind of treatments, or targets for treatment, that can be neuron-protective in the stroke situation, could be envisaged as the most efficient considering the complexity of the pathological process?

The only treatment today (except mechanical removal of clot) is the use of recombinant tissue plasminogen activator (rt-PA). To our understanding even thou ischemic stroke is approximately 85% of the cases compared to hemorrhagic (10%) only a fraction of the ischemic patients are being treated with rt-PA. Improved thrombolytic drugs are being developed to improve half-life and with higher fibrin-specificity to improve this drug. It seems to be essential also for efficient treatment with a neuron-protective agent – that the blood-flow will be restored as soon as possible. What is happening in this area of research and clinical development?

What new biomarkers are being identified for neuropathic pain?

Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.
In October Medivir announced that MIV-247 has been selected as a candidate drug (CD) from its cathepsin S inhibitor project for the treatment of neuropathic pain, and is entering non-clinical development. MIV-247 is a potent and highly selective inhibitor of cathepsin S. Cathepsin S has been shown to be an enzyme that is important for the maintenance of the neuropathic pain state, through its action in releasing fractalkine (a pro-inflammatory protein) in areas of the spinal cord important for pain sensation. Compounds from Medivir’s cathepsin S inhibitor project, including MIV-247, have shown good efficacy in experimental models of neuropathic pain, with no evidence of tolerance induction in longer-term studies.

There are challenges in clinical studies for neuropathic pain and ~ 50% failure rate in phase II clinical studies, despite efficacy in preclinical models of neuropathic pain. What are the key factors to improve the success rate in clinical studies?

Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.
In October Medivir announced that MIV-247 has been selected as a candidate drug (CD) from its cathepsin S inhibitor project for the treatment of neuropathic pain, and is entering non-clinical development. MIV-247 is a potent and highly selective inhibitor of cathepsin S. Cathepsin S has been shown to be an enzyme that is important for the maintenance of the neuropathic pain state, through its action in releasing fractalkine (a pro-inflammatory protein) in areas of the spinal cord important for pain sensation. Compounds from Medivir’s cathepsin S inhibitor project, including MIV-247, have shown good efficacy in experimental models of neuropathic pain, with no evidence of tolerance induction in longer-term studies.

How is the usefulness/validity of human pain models as an early signal of efficacy?

Why are the myeline-active T-cells not eliminated in the thymic selection process?

What triggers Multiple Sclerosis?

What are the problems with current diagnostic techniques within CNS disorders?

Today Mercodia is a world-leading developer, manufacturer and distributor of high quality immunoassay kits. We specialize in ELISA assays for clinical as well as research applications, notably within diabetes, obesity and cardiovascular disease. We offer assays applicable in both human and animal models. CNS disorders is an interesting disease area for us, and we want to learn more about the diagnostic challenges within CNS disorders.

What new biomarkers and technologies are being identified for CNS diseases and what are their benefits over existing biomarkers/technologies? How can these be developed into routine assays that benefit patients for example by stratifying patients for treatment regimes?

Today Mercodia is a world-leading developer, manufacturer and distributor of high quality immunoassay kits. We specialize in ELISA assays for clinical as well as research applications, notably within diabetes, obesity and cardiovascular disease. We offer assays applicable in both human and animal models. CNS disorders is an interesting disease area for us, and we want to learn more about the diagnostic challenges within CNS disorders.

How can companies, academics and clinical researchers collaborate better on new diagnostic tools in order to compare them with existing routine measurements and correlate the data generated to clinical outcomes?

Today Mercodia is a world-leading developer, manufacturer and distributor of high quality immunoassay kits. We specialize in ELISA assays for clinical as well as research applications, notably within diabetes, obesity and cardiovascular disease. We offer assays applicable in both human and animal models. CNS disorders is an interesting disease area for us, and we want to learn more about the diagnostic challenges within CNS disorders.

Do you see any ethical issues with a diagnostics from CSF for prodromal or mild to moderate Alzheimers, being available as an registered In-Vitro Diagnostic?

These questions ask for the scientists view on the clinical need for, and the perceived value of, developing biomarkers for Alzheimers disease.

Where do you see the value of a diagnostic from cerebrospinal fluid (CSF) for prodromal and for mild to moderate Alzheimers (aB42, Tau/pTau), respectively, in absence of a treatment?

These questions ask for the scientists view on the clinical need for, and the perceived value of, developing biomarkers for Alzheimers disease.

Are there species differences in the Blood brain barrier between mouse and man? If yes, what are the differences and the consequences of the differences?

Is there a receptor-mediated passage of proteins across the BBB?

Is the integrity of the BBB affected in degenerative diseases?

In neurodegenerative diseases, how important are autoimmune mechanisms for disease development and progression?

There seems to be an increasing number of publications regarding detection of autoimmune reactions in neurodegenerative diseases. Are these the cause for or results of the diseases.

Are there evidence for autoantibodies as risk markers for neurodegenerative disorders?

The measurement of autoantobodies is an important part of autoimmune diseases. Evidence for autoantibodies in neurodegenerative diseases could make detection an measurement important diagnostic tests.