[ExI] Low-dose lithium stops disease progression in a transgenic rat model of Alzheimer's disease
avant at sollegro.com
Mon Jan 27 01:28:37 UTC 2020
This looks encouraging, since lithium is already a drug prescribed for
mood disorders and the dosage for Alzheimer's is much lower than the
currently used dosage. Of course they still need to conduct human
clinical trials for efficacy. But hope is hope.
There remains a controversy in scientific circles today regarding the
value of lithium therapy in treating Alzheimer’s disease. Much of this
stems from the fact that because the information gathered to date has
been obtained using a multitude of differential approaches,
conditions, formulations, timing and dosages of treatment, results are
difficult to compare. In addition, continued treatments with high
dosage of lithium render a number of serious adverse effects making
this approach impracticable for long term treatments especially in the
In a new study, however, a team of researchers at McGill University
led by Dr. Claudio Cuello of the Department of Pharmacology and
Therapeutics, has shown that, when given in a formulation that
facilitates passage to the brain, lithium in doses up to 400 times
lower than what is currently being prescribed for mood disorders is
capable of both halting signs of advanced Alzheimer’s pathology such
as amyloid plaques and of recovering lost cognitive abilities. The
findings are published in the most recent edition of the Journal of
Building on their previous work
“The recruitment of Edward Wilson, a graduate student with a solid
background in psychology, made all the difference,” explains Dr.
Cuello, the study’s senior author, reflecting on the origins of this
work. With Wilson, they first investigated the conventional lithium
formulation and applied it initially in rats at a dosage similar to
that used in clinical practice for mood disorders. The results of the
initial tentative studies with conventional lithium formulations and
dosage were disappointing however, as the rats rapidly displayed a
number of adverse effects. The research avenue was interrupted but
renewed when an encapsulated lithium formulation was identified that
was reported to have some beneficial effects in a Huntington disease
Lithium in doses up to 400 times lower than what is currently being
prescribed for mood disorders is capable of both halting signs of
advanced Alzheimer’s pathology such as amyloid plaques and of
recovering lost cognitive abilities.
The new lithium formulation was then applied to a rat transgenic model
expressing human mutated proteins causative of Alzheimer’s, an animal
model they had created and characterized. This rat develops features
of the human Alzheimer’s disease, including a progressive accumulation
of amyloid plaques in the brain and concurrent cognitive deficits.
Microdoses of lithium at concentrations hundreds of times lower than
applied in the clinic for mood disorders were administered at early
amyloid pathology stages in the Alzheimer’s-like transgenic rat. These
results were remarkably positive and were published in 2017 in
Translational Psychiatry and they stimulated us to continue working
with this approach on a more advanced pathology,” notes Dr. Cuello.
Encouraged by these earlier results, the researchers set out to apply
the same lithium formulation at later stages of the disease to their
transgenic rat modeling neuropathological aspects of Alzheimer’s
disease. This study found that beneficial outcomes in diminishing
pathology and improving cognition can also be achieved at more
advanced stages, akin to late preclinical stages of the disease, when
amyloid plaques are already present in the brain and when cognition
starts to decline.
“From a practical point of view our findings show that microdoses of
lithium in formulations such as the one we used, which facilitates
passage to the brain through the brain-blood barrier while minimizing
levels of lithium in the blood, sparing individuals from adverse
effects, should find immediate therapeutic applications,” says Dr.
Cuello. “While it is unlikely that any medication will revert the
irreversible brain damage at the clinical stages of Alzheimer’s it is
very likely that a treatment with microdoses of encapsulated lithium
should have tangible beneficial effects at early, preclinical stages
of the disease.”
Dr. Cuello sees two avenues to build further on these most recent
findings. The first involves investigating combination therapies using
this lithium formulation in concert with other interesting drug
candidates. To that end he is pursuing opportunities working with Dr.
Sonia Do Carmo, the Charles E. Frosst-Merck Research Associate in his
He also believes that there is an excellent opportunity to launch
initial clinical trials of this formulation with populations with
detectable preclinical Alzheimer’s pathology or with populations
genetically predisposed to Alzheimer’s, such as adult individuals with
Down Syndrome. While many pharmaceutical companies have moved away
from these types of trials, Dr. Cuello is hopeful of finding
industrial or financial partners to make this happen, and, ultimately,
provide a glimmer of hope for an effective treatment for those
suffering from Alzheimer’s disease.
Reference: “NP03, a Microdose Lithium Formulation, Blunts Early
Amyloid Post-Plaque Neuropathology in McGill-R-Thy1-APP Alzheimer-Like
Transgenic Rats,” by Edward N. Wilson, Sonia Do Carmo, Lindsay A.
Welikovitch, Hélène Hall, Lisi Flores Aguilar, Morgan K. Foret, M.
Florencia Iulita, Dan Tong Jia, Adam R. Marks, Simon Allard, Joshua T.
Emmerson, Adriana Ducatenzeiler and A. Claudio Cuello, 16 December
2019. Journal of Alzheimer’s disease.
More information about the extropy-chat