Nilotinib and Parkinson's Disease

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Nilotinib and Parkinson's Disease
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• Nilotinib For Parkinson's, Nilotinib Parkinson

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Latest update - Research on NILOTINIB drug for
treatment of ALZHEIMERS / PARKINSONS Disease
A New Use for Nilotinib... Oncology Times
January 10th, 2016 - Volume 38 - Issue 1 - p
32 doi 10.1097/01.COT.0000479762.08172.57 News Ty
rosine kinase inhibitors (TKIs) have changed the
treatment paradigm for patients with chronic
myelogenous leukemia (CML), and new research
suggests one of the agents could potentially do
the same for patients with Parkinson's disease.
Researchers found that nilotinib (marketed as
Tasigna by Novartis)approved by the U.S. Food
and Drug Administration for the treatment of
patients with CML (OT 7/10/10 issue)improved
cognition, motor skills, and non-motor function
for patients with Parkinson's disease and Lewy
body dementia. Complete data from the Phase I
clinical trial were presented at the Annual
Meeting of the Society for Neuroscience in
October (Program 12,Poster1
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When used in higher doses for CML, nilotinib
forces cancer cells into autophagya biological
process that leads to the death of tumor cells,
study coauthor Charbel Moussa, MD, PhD, Director
of Georgetown's Laboratory of Dementia and
Parkinsonism, explained in a news release. The
dose used in CML treatment is significantly
higher than what we used in our Parkinson's
study. It appears that in smaller doses once a
day, nilotinib turns on autophagy for about four
to eight hourslong enough to clean out the cells
without causing cell death. Then proteins that
build up again will be cleared when the drug is
given again the next day. The observed efficacy
in cognition, motor skills, and non-motor
function improvement (such as constipation) for
many patients was the most dramatic result, the
researchers reported, according to the news
release. One individual confined to a wheelchair
was able to walk again three others who could
not talk were able to hold conversations.
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Study Details The study included 11 patients with
advanced Parkinson's disease, Parkinson's disease
with dementia, or Lewy body dementia, who
received 150 to 300 mg nilotinib daily for six
months. All patients benefited from the drug, and
10 had clinically meaningful improvements.
Patients also showed positive changes in relevant
cerebrospinal fluid biomarkers of Parkinson's,
including alpha-synuclein (a-synuclein), amyloid
beta-40/42 (Abeta-40/42), and dopamine, with
statistically significant changes in total Tau
and p-Tau. Prior studies show that a-synuclein
and Abeta 40/42 in cerebrospinal fluid are
decreased as Parkinson's worsens, while Tau and
p-Tau are increased in cerebrospinal fluid with
the onset of dementia. The changes in Tau,
p-Tau, a-synuclein and Abeta-40 and 42 in spinal
fluid suggest the clearance of toxic proteins in
the brain, another study coauthor Fernando
Pagan, MD, a Georgetown University Medical Center
Associate Professor of Neurology and Director of
the Movement Disorders Program at MedStar
Georgetown University Hospital, said, also in a
news release.
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To my knowledge, this study represents the first
time a therapy appears to reverseto a greater or
lesser degree depending on stage of
diseasecognitive and motor decline in patients
with these neurodegenerative disorders, Pagan
added. But it is critical to conduct larger and
more comprehensive studies before determining the
drug's true impact. No serious side effects were
reported and the drug was well tolerated by the
patients on the trial. Why Try a Cancer
Drug? Moussa's preclinical research led him to
think about using cancer drugs to treat
neurological disorders. He was looking for an
FDA-approved drug that could penetrate the
blood-brain barrier and turn on the garbage
disposal machinery inside neurons to clear toxic
intracellular proteins and prevent their
accumulation within, or secretion outside of,
brain cells, he noted. Moussa is an inventor on a
Georgetown University patent application for use
of nilotinib and other tyrosine kinase inhibitors
for the treatment of neurodegenerative disease.
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At the end of this study patients were given the
option to continue taking nilotinib (provided by
Novartis) as part of an expanded access study.
Moussa and other Georgetown researchers are now
planning larger clinical trials with nilotinib
for patients with Parkinson's and other similar
diseases including Alzheimer's disease, likely to
begin in 2016. Source- https//journals.lww.com/o
ncology-times/fulltext/2016/01100/A_New_Use_for_Ni
lotinib___.12.aspx Copyright 2016 Wolters
Kluwer Health, Inc. All rights reserved.
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NEW CLINICAL TRIAL WILL TEST CANCER DRUG AS
ALZHEIMERS TREATMENT - September 29, 2016 The
Alzheimers Drug Discovery Foundation (ADDF)
announces a 2.1 million grant awarded to R.
Scott Turner, MD, PhD, of Georgetown University
Medical Center to conduct a phase II clinical
trial of low-dose nilotinib (marketed as Tasigna
for use as a cancer therapy) in patients with
Alzheimers disease. Nilotinib is an FDA-approved
drug for the treatment of adult chronic myeloid
leukemia. In preclinical studies conducted by
Georgetown researchers, nilotinib reduced
cognitive impairment by targeting two of the
underlying causes of Alzheimersneuroinflammation
and misfolded proteins. Nilotinib triggers a
process (called autophagy) that removes the toxic
proteins tau and beta-amyloid from the brain
before they accumulate into plaques and tangles.
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Dr. Turner, co-medical director of Georgetown
University Medical Centers Translational
Neurotherapeutics Program (TNP) and director of
the Georgetown Memory Disorders Program, says,
By stimulating the brains normal autophagic
process, which clears out these misfolded
proteins in cells, we hope to prevent or slow the
progression of Alzheimers. In fact, nilotinib
may be a firsta broad-spectrum
anti-neurodegenerative drug that targets all
misfolded protein aggregates that accumulate in
the brain of Alzheimers patients. By targeting
both amyloid and tau, this study may point the
way to a new strategy in Alzheimers disease
treatment. The preclinical research was
conducted by Charbel Moussa, MD, PhD, scientific
and clinical research director for Georgetowns
TNP, who explains, Nilotinib seems to activate
the cells garbage disposal machine, reduce
plaques and tangles and reverse cognitive decline
in animal models of Alzheimers disease. We hope
that this trial will clarify the effects of
nilotinib in Alzheimers patients. Moussa will
be a co-investigator on the Alzheimers trial.
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The trial is expected to start this year and will
include 42 patients, with half randomized to
receive an escalating dose of nilotinib, while
the other half receives a placebo. The primary
objectives of the study will be to test the
drugs safety and tolerability and to measure
whether nilotinib reduces inflammation and the
presence of beta-amyloid and tau in spinal fluid.
Dr. Turner and his colleagues in the Georgetown
Memory Disorders Program will also perform
cognitive and functional abilities tests. Dr.
Howard Fillit, Founding Executive Director and
Chief Science Officer of the ADDF, says The
ADDF is proud to support a clinical trial that
holds such promise for Alzheimers patients. This
funding is part of our wider initiative to use
the knowledge gained from cancer research to
advance effective treatments for
Alzheimers. The ADDFs initiative Learning
from Cancer to Advance Treatments for
Neurodegenerative Diseases launched in 2015 with
a conference held in partnership with the New
York Academy of Sciences. Its goal is both to
develop new therapies and test existing cancer
therapies for their potential in treating
Alzheimers disease. In addition to the nilotinib
trial at Georgetown, this initiative includes
funding for drug development projects at Oryzon
Genomics, Rodin Therapeutics, and Yuma
Therapeutics.

Source- https//www.alzdiscovery.org/news-room/ann
ouncements/new-clinical-trial-will-test-cancer-dru
g-as-alzheimers-treatment
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