The blood-brain barrier normally prevents biopharmaceuticals from entering the brain and so treating a disease such as Alzheimer's - caused by the death of neurons - is normally the preserve of small molecules drugs. However, that could all be about to change. While investigating how the Nogo66 receptor (NgR1) helps repair neurons in spinal cord injury, scientists at Biogen Idec made a startling discovery: it also swallows up beta-amyloid peptide, which is the main constituent of amyloid plaques that accumulate at abnormal levels in the brain of Alzheimer's sufferers. The plaques cause nerve cells to die and this, in turn, causes the symptoms of the disease, including loss of memory, an inability to learn, make judgments and perform day-to-day tasks. Dr Daniel Lee, a neurobiologist at Biogen Idec, explained to delegates at the recent Drug Discovery and Development of Innovative Therapeutics (DDT) conference in Boston, that he and his colleagues at the biotech company had been investigating the ability of NgR1 to seemingly initiate axon regeneration in the central nervous system (CNS). However, he said: "A lot of companies are not interested in spinal cord injury [drugs] and we so were looking for different indications, for example as a treatment after stroke." As it became increasingly clear that axon destruction (axonopathy) was important in Alzheimer's disease, the researchers became more and more interested in this indication. Lee said: "Way before and when a patient is starting to get plaques, they are already showing signs of axonopathy. So we asked ourselves, could a therapy for axonopathy be used to regenerate or generate new axons and help with the functional recovery of Alzheimer's?" He was also quick to point out that the therapy cannot help with plaque removal. As the scientists delved deeper in NgR1 biology, including its structure, they discovered it also binds to beta-amyloid. They decided to test the theory in an animal model. They created a therapeutic by taking a portion of the NgR1 and fusing it to immunoglobulin 1 (IgG1), called sNgR310-Fc. When this molecule was subcutaneously administered to transgenic Alzheimer's mouse brains, Lee said not only did it promote nerve repair, it also reduced both beta-amyloid and plaque levels. This resulted in an improvement in memory function in the same disease model. As Lee explained, this dual-acting mechanism sets the drug apart from anti-beta-amyloid antibodies, with which he admits it cannot compete. When asked how he they had delivered the potential drug in tests, Lee admitted: "Peripheral administration of the protein still seems to go to the brain; it shouldn't, but it does."