Tech Review

Evolved treatments for Alzheimer’s

06.03.2012

Zurich-based NeurImmune AG follows unconventional routes – for example, the company doesn’t rely on VC investors. And Neurimmune has also turned the drug discovery process upside down by taking its drug candidates from healthy humans that have developed an immune response to pathogenic proteins like Abeta. Biogen Idec is building on NeurImmune’s expertise, and has already signed two agreements.

The deposition of pathogenic protein aggregates derived from physiological brain proteins is a common theme underlying most neurodegenerative diseases. These protein clusters deposited in the brains of human patients include, for example, Abeta (Ab)and tau in Alzheimer’s disease and Down syndrome, a-synuclein in Parkinson’s disease and dementia with Lewy bodies, and super­oxide dismutase 1 in amyotrophic lateral sclerosis. Disease-causing mutations in the genes encoding these proteins point to their central roles in the etiology of neuro­degeneration. Both genetic and the more frequent “sporadic” variants of neurodegeneration are associated with the conversion of misfolded physiological proteins into pathogenic aggregates.
Prion-like mechanism
Synaptic connections by which neuronal networks communicate are among the most vulnerable structures affected, result­ing in the progressive deterioration of neuronal network activities. When released from affected cells, the pathogenic aggregates can enter unaffected neighbouring cells, bind to their cognate physiological protein counterparts, and force them to adopt pathological conformations as well. This thermodynamically driven process of prion-like infectivity drives the spatiotemporal spreading of protein aggregation from cell to cell and throughout the central nervous system. Unexpectedly, this metamorphosis from physiologic to pathogenic structural conformations of endogenous proteins can be accompanied by humoral immune responses generating B-cells encoding high-affinity antibodies that specifically bind and neutralise such pathogenic protein aggregates. This observation provides a basis for asking the questions of how healthy elderly subjects succeed in preserving intact cognitive functions during aging, and how such knowledge can be used pharmacologically to prevent neurodegeneration in subjects at risk. Neur­Immune studied immune responses directed against pathogenic protein aggregates in cohorts of healthy elderly subjects with either excellent cognitive performance or recovery from initial signs of cognitive decline. Up to 80% of healthy elderly subjects had established B-cell memory against aggregated Ab, thus allowing for the cloning of human monoclonal antibodies targeting these aggregates. Recombinantly produced human monoclonal antibodies with high affinity and selectivity for aggregated Ab crossed the blood-brain barrier in transgenic mouse models of Alz­heimer’s disease and accumulated on Ab deposits in the brain. Brain-resident microglial cells were recruited to antibody-labeled aggregates, and removed them by means of phagocytosis paralleled by signs of neuronal recovery and restored behavioral functions. The pharmacological effects of these human monoclonal antibodies are currently being studied in human patients with early signs of cognitive decline. In addition to immune responses against aggregated Ab, healthy elderly subjects also mounted immune responses against misfolded or aggregated forms of a-synuclein, superoxide dismutase 1, tau and TAR DNA-binding protein 43. The corresponding high affinity human monoclonal antibodies were cloned, sequenced, produced recombinantly and validated in vitro and in vivo. As an example, chronic treatment of transgenic mice with signs of amyotrophic lateral sclerosis established rescue of alpha-motor neurons along with increased overall survival. Likewise, recombinant human antibodies against a-synuclein decreased alpha-synuclein pathology and improved motor functions in transgenic mouse models of Parkinson’s disease. Pharmacological intervention using recombinant human antibodies against disease-causing toxic protein aggregates provides a promising concept for the treatment and prevention of neurodegeneration.
In November 2007, Biogen Idec closed a first partnership with NeurImmune for the development of antibodies to treat Alz­heimer’s disease. Neurimmune could receive an aggregate of US$380m in up-front and success-based milestone payments. In December 2010, Biogen acquired a Neur­Immune subsidiary that contained the global rights to three preclinical candidates targeting neurodegenerative diseases.

Politics / Law

23.03.2012

Brussels/Strasbourg – Health claims are set to be drastically limited in the EU. On Wednesday 21 March the Environment Committee of the European Parliament confirmed a proposal of the European Commission to prohibit 1,600 health...

Politics / Law

15.03.2012

Parma/Stockholm – Foodborne bacteria such as Salmonella and Campylobacter are becoming more and more resistant to antimicrobial drugs, according to a joint report published by the European food watchdog EFSA and the European...

BioFunding

09.03.2012

In mid-February, scientists and entrepreneurs from nine EU countries met at the Center for Genomic Regulation (CRG) in Barcelona to launch the 4DCellFate project. Positioned within the FP7 Programme, the consortium will receive...

BioFunding

09.03.2012

Brussels – The EU’s Innovative Medicines Initiative (IMI) will establish the European Lead Factory, an EU-wide public-private partnership aiming to facilitate drug discovery efforts. The Lead Factory will comprise a...

Editorial

07.03.2012

T    he societal and economic challenges facing Europe and the world are complex and interconnected. The Bioeconomy Strategy and Action Plan “Innovating for Sustainable Growth: a Bioeconomy for Europe”, which was adopted by the...

Tech Review

07.03.2012

Intellectual Property (IP) is without question one of the most vital aspects of any bio­tech venture, a key and undisputed factor for success. However, most bio­tech companies are still incapable of unlocking the value of their...

Clinical Trial

07.03.2012

Schlieren – Swiss Cytos Biotechnology Ltd. has been authorised to restructure a convertible bond by Canton of Zurich authorities. The company does not have enough cash to pay it back. Negotiations with bond holders failed in a...

Clinical Trial

06.03.2012

Munich – German 4SC AG jumped 39% to €2.05/share after oncology drug candidate resminostat met the primary endpoint of at least a 20% progression-free survival rate in a Phase II trial to treat patients with hepatocellular...

Editorial

06.03.2012

The start of 2012 witnessed the tides turning in favour of small and mid-cap names in the European Life Sciences sector. Major global biotechnology indices like the NBI, BTK, and BIOTK are up over 15% year to date. The pace of...

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