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Implant Developed to Deliver Alzheimer’s Immunotherapy

Brain wiring illustration

Brain wiring illustration (Courtesy, Human Connectome Project and NIH)

18 March 2016.  A neuroscience team from Ecole polytechnique fédérale de Lausanne, or EPFL, in Switzerland designed and implanted a capsule that in lab mice generates antibodies to reduce amyloid beta plaque accumulations in the brain associated with Alzheimer’s disease. Researchers from the lab of Patrick Aebischer, also EPFL’s president, published its findings in the 8 March issue of the journal Brain (paid subscription required).

Alzheimer’s disease is progressive neurodegenerative disease affecting growing numbers of older people worldwide. People with Alzheimer’s disease often have deposits of abnormal substances in spaces between brain cells, known as amyloid-beta peptides, as well as misfolded tangles of proteins inside brain cells known as tau. Amyloid-beta peptides accumulate in spaces between brain cells in aggregate formations known as oligomers.

As the oligomer accumulations enlarge and become plaques they interfere with synapses and receptors on neighboring cells, affecting their ability to function. It is not yet conclusively established, however, if amyloid-beta deposits are the result of Alzheimer’s disease or a cause of it. But the authors cite previous studies indicating monoclonal or targeted antibodies directed against amyloid-beta accumulations before they become plaques and symptoms develop may prevent irreversible brain damage.

Aebischer and colleagues, including associates from the pharmaceutical company Roche and the particle beam accelerator Swiss Light Source, also cite previous research showing repeated vaccine injections of antibodies cause adverse side effects, calling for a different approach that provides continuous delivery of antibodies that fight amyloid-beta deposits. The team’s method is a small (27 x 12 x 1.2 millimeters) capsule made of biocompatible materials and implanted under the skin that produces and delivers antibodies into the blood stream over a period of time, a technology Aebischer and colleagues described in a 2014 publication.

The researchers developed genetically engineered cells from muscle tissue producing antibodies that specifically tag and target amyloid-beta proteins, contained in a supporting hydrogel medium that keeps them active. The capsule containing the cells and hydrogel is made of biocompatible polymers with two membranes that protect the contents, but still allow the antibodies produced inside to flow into the blood stream. The capsule’s construction also shields the contents from the recipient’s immune system, thus preventing rejection.

The team implanted the capsules under the skin of lab mice, genetically altered to express amyloid-beta and tau in their brains, but before the proteins became plaque deposits. The results show after 39 weeks, mice receiving the capsules showed sharply reduced amyloid-beta loads in their brains, as well as tau proteins that are not activated as found in cases of Alzheimer’s disease. Similar mice not given the capsules develop amyloid-beta plaque and tau deposits characteristic of Alzheimer’s. No serious adverse effects in the mice were reported.

The proof-of-concept study, say the authors, supports the use and further development of these implanted immunotherapy capsules as passive preventive therapies in early diagnosed cases of Alzheimer’s and perhaps other neurodegenerative disorders. The following video offers an animated description of EPFL’s invention.

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