March 2019 digital v1

esearch snippets
Fibrinogen induces spine
elimination in Alzheimer’s
Mario Merlini et al unveiled
the role of the blood-clotting
protein fibrinogen in blood in
causing the characteristic cognitive
decline of Alzheimer’s disease.
Cerebrovascular alterations are a
key feature of Alzheimer’s disease
(AD) pathogenesis. The researchers
used state-of-the-art imaging
technology to produce the first
three-dimensional volume images
of Alzheimer’s disease. The images
of the brains of patients with
Alzheimer’s disease and mouse
models were studied. The bloodprotein
fibrinogen was seen to leak
from the blood into the brain, where
it activated the brain’s immune
cells triggering them to destroy
neuronal synapses. Fibrinogen then
induces spine elimination leading
to cognitive deficits mediated by
CD11b-CD18 microglia activation.
Fibrinogen-induced spine elimination
was prevented by inhibiting
reactive oxygen species (ROS)
generation or by genetic elimination
of CD11b. In the mouse models,
this genetic elimination showed
to reduce neuroinflammation,
synaptic deficits and cognitive
decline. The research thus unveils
that fibrinogen-induced spine
elimination and cognitive decline
via CD11b leads to cerebrovascular
damage with immune-mediated
neurodegeneration and may have
important implications in AD and
related conditions.
Source: Neuron Feb 5,t 2019 DOI: https://doi.
org/10.1016/j.neuron.2019.01.014
Ovarian cyst surgery
often unnecessary
Wouter Froyman et al shows
evidence promoting a watchful
waiting approach towards non-cancerous
ovarian cyst. The researchers performed
a two-year study involving 1919 women
from 10 different countries, including
the UK, Belgium, Sweden and Italy, who
were diagnosed with non-cancerous
ovarian cysts. The average age of the
women in the study was 48, and the
average size of the cyst was 4cm. Out of
the 1919 women in the trial, 20 percent
had cysts that disappeared of their
own accord, and 16 percent underwent
surgery. Overall, in 80 percent of cases
either the cyst resolved or did not need
intervention. Only 12 women were
subsequently diagnosed with ovarian
cancer, making the risk of cancer 0.4
percent. The rate of other complications,
such as ovarian twisting or cyst rupture
was 0.4 percent and 0.2 percent
respectively. The researchers suggest
that the risk of malignancy and acute
complications is low if adnexal masses
with benign ultrasound morphology are
managed conservatively, invasive surgical
procedures can be avoided.
Source: The Lancet Oncology February 05, 2019
https://doi.org/10.1016/S1470-2045(18)30837-4
Oral delivery of insulin
via ingestible capsule
A
bramson et al. developed an
ingestible drug delivery vehicle that
can be used for oral administration
of insulin. The capsule is designed
to be able to self-reorient from any
starting position so as to attach to
the gastric wall. This ingestible selforienting
millimeter-scale applicator
(SOMA) autonomously positions itself
with the gastrointestinal tissue. Within
the capsule, a needle is attached to a
compressed spring that is held in place
by a disk made of sugar which gets
dissolved on reaching the stomach.
It then deploys its needles fabricated
from active pharmaceutical ingredients
directly through the gastric mucosa while
avoiding perforation and delivers the
active pharmaceutical ingredient. The
approach successfully provided active
insulin delivery in pigs and rat models.
56 / FUTURE MEDICINE / March 2019