A CURE FOR

ALZHEIMERS

What is Alzheimer's disease?

Alzheimers disease is an irreversible, progressive brain
disorder that slowly destroys memory and thinking skills
and, eventually, the ability to carry out the simplest tasks.
In most people with Alzheimers, symptoms first appear in
their mid-60s. Alzheimers disease is the most common
cause of dementia among older adults.
In 1906, Dr. Alzheimer noticed changes in the brain
tissue of a woman who had died of an unusual mental
illness. Her symptoms included memory loss, language
problems and unpredictable behavior. After she died, he
examined her brain and found many abnormal clumps (now
called amyloid plaques) and tangled bundles of fibers (now
called neurofibrillary, or tau tangles).

What happens to the

brain
in
Alzheimer's
disease?
Scientists
continue
to
unravel the complex brain
changes involved in the
onset and progression of
Alzheimers
disease.
It
seems likely that damage
to the brain starts a
decade or more before
memory
and
other
cognitive
problems
become evident. During
this preclinical stage of
Alzheimers
disease,
people
seem
to
be
symptom-free, but toxic
changes are taking place
in the brain.

The damage initially appears to take place in the

hippocampus, the part of the brain essential in
forming memories. As more neurons die, additional
parts of the brain are affected. By the final stage of
Alzheimers, damage is widespread, and brain tissue
has shrunk significantly.

Alzheimers is
currently ranked as
the sixth leading
cause of death in the
United States, but
recent estimates
indicate that the
disorder may rank
third, just behind
heart disease and
cancer, as a cause of
death for older
people.

What is dementia?
Dementia is the loss of cognitive functioningthinking,
remembering, and reasoningand behavioral abilities to such an
extent that it interferes with a persons daily life and activities.
Dementia ranges in severity from the mildest stage, when it is just
beginning to affect a persons functioning, to the most severe stage,
when the person must depend completely on others for basic
activities of daily living.

Scientists know that Alzheimers progresses on a spectrum

with three stagesan early, preclinical stage with no
symptoms; a middle stage of mild cognitive impairment (MCI);
and a final stage of Alzheimers dementia. At this time,
doctors cannot predict with any certainty which people with
MCI will or will not develop Alzheimers.

The onset of Alzheimers disease is thought by many to

be related to the deposition of high concentrations of
amyloid beta protein within the brain. If true, and theres
considerable evidence that it probably is, preventing the
accumulation of amyloid beta may slow down or reverse
the onset of Alzheimers.

In a brilliant move, researchers at the cole Polytechnique

Fdrale de Lausanne in Switzerland created an implantable
device that contains live cells that produce anti amyloid
beta antibodies.
.

Amazingly, this was already tested in laboratory mice with

Alzheimers. In two models of the disease, the implants
significantly reduced the accumulation of amyloid beta in
the mice brains compared to controls.
Indeed, the constant flow of antibodies produced by the
capsule over a course of 39 weeks prevented the
formation of Abeta plaques in the brain. The treatment
also reduced the phosphorylation of the protein tau,
another sign of Alzheimers observed in these mice.

A bioactive capsule containing

cells that have been genetically
engineered to produce antibodies
against Abeta proteins. The
capsule is implanted in the tissue
under the skin, and over time the
cells produce and release a steady
flow of antibodies into the
bloodstream, from where they
cross over into the brain to target
the Abeta plaques.

The capsule is based on a design which is referred to as a

macroencapsulation device and it is made of two
permeable membranes sealed together with a
polypropylene frame. The completed device is 27-mm long,
12-mm wide and 1.2-mm thick, and contains a hydrogel that
facilitates cell growth. All the materials used are
biocompatible, and the lab specifically used a method that is
easily reproducible for large-scale manufacturing.

The cells inside the capsule are important. Not only must
they be able to produce antibodies, but they also have to be
compatible with the patient, so as to not trigger the immune
system against them, like a transplant can. This is where the
capsules membranes come into play, shielding the cells
from being identified and attacked by the immune system.
This protection also means that cells from a single donor can
be used on multiple patients.

The proof-ofconcept work is a

landmark. It
demonstrates
clearly that
encapsulated cell
implants can be
used successfully
and safely to deliver
antibodies to treat
Alzheimers disease
and other
neurodegenerative
disorders that
feature defective
proteins.

Elena-Andrada Szebeni
Diana Runcan