Bioarctic Neuroscience AB

Stockholm, Sweden

Bioarctic Neuroscience AB

Stockholm, Sweden

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Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-15-2014 | Award Amount: 13.98M | Year: 2015

Today there is no regenerative therapy available for treatment of complete spinal cord injuries (SCI). BioArctic Neuroscience develops a novel treatment of complete SCI. The method is based on the regeneration of functional nerves in the injured spinal cord. Nerve grafts are transplanted into the injured spinal cord, by using a biodegradable device, loaded with a growth factor and nerve grafts (these three components are abbreviated SC0806). Efficacy and safety of the treatment has been demonstrated in an in vivo model of SCI. The therapy has been designated Orphan Drug status in Europe and in USA. Ethical approval to commence into clinical trial in Sweden was recently granted. The proposed project is the first clinical trial of the treatment of complete spinal cord injury. Following surgery at the Karolinska University Hospital, patients will receive rehabilitation in their home countries, with state of the art robotics equipment, at clinics in Denmark, Finland and Sweden. This clinical study will be the first in-human trial with this new treatment concept. Several interim analyses are included in the study design to secure the safety of the patients. This is a single dose study in up to 3 sequences (A, B and C) in 27 subjects with complete traumatic SCI. In the first sequence (A), 6 subjects will be randomized to a surgical procedure where SC0806 will be implanted at the spinal cord, and receive robotics assisted walking training for 18 months, and 3 subjects will be randomized to specific walking training only. For safety reasons, the first three subjects will be operated on and implanted with at least 1 month in between. If efficacy is demonstrated, control subjects from (A) and (B) and (C) will later be given the opportunity to receive treatment with SC0806.The proposed project spans a period of 42 months and will start nov 2014 with screening, inclusion and treatment of patients in Sweden.


Antibodies and fragments thereof have high affinity for human -synuclein protofibrils and low binding of -synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting -synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with -synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with -synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with -synuclein pathology, and in methods for reducing or inhibiting -synuclein aggregation by administration of such an antibody or fragment.


Antibodies and fragments thereof have high affinity for human -synuclein protofibrils and low binding of -synuclein monomers, wherein the antibodies or fragments have specified Complementarity Determining Region (CDR) sequences. Compositions comprise such an antibody or fragment and methods of detecting -synuclein protofibrils use such an antibody or fragment. In further embodiments, methods of preventing, delaying onset of or treating a neurodegenerative disorder with -synuclein pathology comprise administering such an antibody or fragment, and such an antibody or fragment is used in the manufacture of a pharmaceutical composition for treatment of a neurodegenerative disorder with -synuclein pathology. Such an antibody or fragment is used in the diagnosis or monitoring of the development of a neurodegenerative disorder with -synuclein pathology, and in methods for reducing or inhibiting -synuclein aggregation by administration of such an antibody or fragment.


An in vivo method for detecting -synuclein protofibrils in human tissue comprises administering an antibody or fragment thereof to a human, wherein the antibody or fragment thereof is labelled with a detectable label, and detecting a complex formed between the antibody or fragment thereof and -synuclein protofibrils in the human tissue. The antibody or fragment thereof has high affinity for human -synuclein protofibrils and low binding of -synuclein monomers and has a combination of three specified variable heavy (VH) CDR sequences and three specified variable light (VL) CDR sequences.


Methods for detecting -synuclein oligomers in vivo comprise administering an antibody to an individual suspected of carrying soluble -synuclein, wherein the antibody is produced from a stabilized soluble -synuclein oligomer and is capable of binding the stabilized soluble -synuclein oligomer, wherein the stabilized soluble -synuclein oligomer has a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer of the -synuclein, and wherein the antibody is labelled with a detectable marker; and detecting the presence of any complex formed between the antibody and soluble -synuclein by detection of the marker.


The invention relates to an isolated monoclonal antibody or antigen-binding fragment thereof that (a) binds (i) wild-type A 42/40 protofibril comprising N-terminal truncated A forms and (ii) A 42/40 Arc protofibril comprising N-terminal truncated A forms and (b) has no or little cross-reactivity to A 42/40 monomers. The invention further relates to a method of using such an antibody to treat Alzheimers disease.


Methods of treating or delaying onset of a neurodegenerative disorder with -synuclein pathology in an individual comprise administering an antibody which is produced from a stabilized soluble -synuclein oligomer and capable of binding a stabilized soluble -synuclein oligomer, the stabilized soluble -synuclein oligomer having a lower formation rate to a non-soluble aggregated form than a non-stabilized soluble oligomer of the -synuclein. The antibody has been collected from a non-human animal to which stabilized soluble -synuclein oligomer had been administered or has been produced by hybridoma technology, phage display, ribosome display, mammalian cell display or bacterial display, and the disorder with -synuclein pathology is characterized by deposition of Lewy bodies and Lewy neurites or is selected from the group consisting of Parkinsons disease (PD), dementia with Lewy bodies (DLB), the Lewy body variant of Alzheimers disease, and multiple system atrophy (MSA).


The invention relates to an isolated monoclonal antibody or antigen-binding fragment thereof that (a) binds (i) wild-type A 42/40 protofibril comprising N-terminal truncated A forms and (ii) A 42/40 Arc protofibril comprising N-terminal truncated A forms and (b) has no or little cross-reactivity to A 42/40 monomers. The invention further relates to a method of using such an antibody to treat Alzheimers disease.


Patent
BioArctic Neuroscience AB and Eisai R&D Management Co. | Date: 2015-07-08

The present invention relates to the amyloid beta peptide (A) and more specifically to antibodies binding to A protofibrils and their use in therapy and/or prophylactic treatment of Alzheimers disease and other disorders associated with A protein aggregation. Further the invention may relate to diagnosis of such diseases as well as monitoring of disease progression by use of the antibodies of the invention. Further, the invention may relate to veterinary use of the antibodies of the invention.


Grant
Agency: European Commission | Branch: H2020 | Program: SME-1 | Phase: PHC-12-2015-1 | Award Amount: 71.43K | Year: 2015

Parkinsons disease (PD) is one of the most prevalent neurodegenerative disorders and a disease with a significant unmet medical need. World-wide, more than 4.6 million individuals over the age of 50 suffer from PD and it is estimated that the number will more than double by 2030. The economic impact of the disease is enormous and the estimated annual European cost of PD is 14 billion euros. At present, only symptomatic therapies are available for PD and there is a huge unmet need for treatments that also slow or halt disease progression. Improved patient outcomes are achieved by early diagnosis and disease modifying treatment. BioArctic Neuroscience is developing a PD biomarker assay, with the potential of becoming the first biochemical biomarker assay that can reflect the underlying pathophysiology of disease. The assay is based on CSF measurements of toxic oligomer/protofibril forms of alpha-synuclein. In this project we will: Conduct biochemical biomarker assay development for PD Conduct a small pilot study on clinical cohorts including patients with PD and healthy controls Evaluate the business opportunities and further development path for PD biomarkers Today, there are no reliable biochemical biomarkers for PD and the disease is often difficult to diagnose. The differential diagnosis of PD is based on clinical features and the golden standard still remains neuropathological confirmation. Misclassification, especially in early PD, occurs frequently. High sensitivity and specificity can only be obtained at specialized centres, and after several years of follow-up. To be able to modify or halt the disease progression it is beneficial to initiate a disease modifying treatment at an earlier stage than what is possible today. The clinical validation of a sensitive and specific biomarker that also could mirror the treatment effect would make an enormous advantage and need to be developed in parallel with the development of new disease modifying therapeutics.

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