NEW RESEARCH SHOWS NEW METHODS FOR TREATING BRAIN DISEASES--

New research study creates new
opportunities for treating brain
diseases.
ppsala Universitet releases nee research suggestions that can br adopted to treat brain problems.
Immunotherapy has proven to be
effective against many serious diseases.
But to treat diseases in the brain, the
antibodies must first get past the
obstacle of the blood-brain barrier. In a
new study, a research group describes
their development of a new antibody
design that increases brain uptake of
antibodies almost 100-fold.

Immunotherapy has proven to be effective against
many serious diseases. But to treat diseases in
the brain, the antibodies must first get past the
obstacle of the blood-brain barrier. In a new
study, a research group at Uppsala University
describes their development of a new antibody
design that increases brain uptake of antibodies
almost 100-fold.
Immunotherapy entails treatment with antibodies; it is the
fastest growing field in pharmaceutical development. In
recent years, immunotherapy has successfully been used
to treat cancer and rheumatoid arthritis, and the results of
clinical studies look very promising for several other
diseases. Antibodies are unique in that they can be
modified to strongly bind to almost any disease-causing
protein. In other words, major potential exists for new
antibody-based medicines.
The problem with immunotherapy for diseases affecting
the brain is that the brain is protected by a very tight layer
of cells, called the blood-brain barrier. The blood-brain
barrier effectively prevents large molecules, such as
antibodies, from passing from the bloodstream into the
brain. It has therefore been difficult to use immunotherapy
to treat Alzheimer's and Parkinson's disease, which affect
the brain, as well as cancerous tumours in the brain.
It has been known for a long time that some large
proteins are actively transported across the blood-brain
barrier. These include a protein called transferrin, whose
primary task is to bind to iron in the blood and then
transport it to the brain. The research group behind this
new study has taken advantage of this process and
modified the antibodies they want to transport into the
brain using components that bind to the transferrin
receptor. Then, like a Trojan horse, the receptor
transports antibodies into the brain. The number of
modifications to and placement of the antibodies have
proven to be important factors for making this process as
effective as possible.
"We've placed them so that each antibody only binds with
one modification at a time, despite being modified in two
places. Our design thus doubles the chances of the
antibody binding to the transferrin receptor compared
with only one modification. We've successfully increased
the amount of antibodies in the brain almost 100-fold,
which is the largest uptake improvement that has ever
been shown," says Greta Hultqvist, researcher at the
Department of Public Health and Caring Sciences at
Uppsala University.
To try out the new format, researchers have used it on an
antibody that binds to a protein involved in the course of
Alzheimer's disease. Without the modification, they could
only detect very small quantities of antibody in the brain
in a mouse model of Alzheimer's disease, while they
could detect high levels of the modified antibody in the
same mice.
"From a long-term perspective, it's likely that the new
format can be used to effectively treat not only
Alzheimer's disease, but also other diseases affecting the
brain," says Dag Sehlin, researcher at the Department of
Public Health and Caring Sciences at Uppsala University.
Story Source:
Materials provided by Uppsala Universitet . Note: Content
may be edited for style and length.
Journal Reference :
1. Greta Hultqvist, Stina Syvänen, Xiaotian T Fang, Lars
Lannfelt, Dag Sehlin. Bivalent Brain Shuttle
Increases Antibody Uptake by Monovalent Binding to
the Transferrin Receptor . Theranostics, 2017; 7 (2):
308 DOI: 10.7150/thno.17155

SOURCE: SCIENCEDAILY