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http://www.clinicaltrials.gov/ct2/show/NCT01035671?term=friedreich&rcv_d=14
Safety and Efficacy Study of A0001 in Subjects With Friedreich's Ataxia
This study is currently recruiting participants.
Verified by Penwest Pharmaceuticals Co., December 2009
First Received: December 17, 2009 Last Updated: December 18, 2009 History of
Changes
Sponsor: Penwest Pharmaceuticals Co.
Information provided by: Penwest Pharmaceuticals Co.
ClinicalTrials.gov Identifier: NCT01035671
Purpose
This is a Phase 2a double-blind, placebo-controlled study with two dose
levels of A0001 given twice daily for 28 days. Potential subjects will be
screened first to determine eligibility, after which they will be randomized
to receive either a high dose of A0001, a low dose of A0001 or placebo for
28 days.
Eligible subjects will return within 21 days of screening for the baseline
visit and randomization to one of three potential treatments. The subjects
will be required to take 3 capsules of study medication in the morning with
a morning meal and 3 capsules of study medication at night with an evening
meal for 28 days. Additional visits to the clinic are planned for Day 14 and
Day 28, at which time a number of clinical and biochemical assessments will
be done.
Condition Intervention Phase
Friedreich's Ataxia
Drug: alpha-tocopherolquinone (A0001)
Drug: placebo
Phase II
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver,
Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment,
Safety/Efficacy Study
Official Title: A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, 28
Day, Three-arm, Parallel Group Study of A0001 in the Treatment of Subjects
With Friedreich's Ataxia
Resource links provided by NLM:
Genetics Home Reference related topics: deoxyguanosine kinase deficiency
Friedreich ataxia Marinesco-Sjögren syndrome mitochondrial
neurogastrointestinal encephalopathy disease
MedlinePlus related topics: Friedreich's Ataxia
U.S. FDA Resources
Further study details as provided by Penwest Pharmaceuticals Co.:
Estimated Enrollment: 42
Study Start Date: December 2009
Estimated Study Completion Date: June 2010
Estimated Primary Completion Date: June 2010 (Final data collection date for
primary outcome measure)
Arms Assigned Interventions
Low Dose: Experimental
A0001 (0.5 g BID) Drug: alpha-tocopherolquinone (A0001)
28 days of low dose (1.0 g total daily dose) oral A0001 capsules. Treatment
taken twice daily with meals.
High Dose: Experimental
A0001 (0.75 g BID) Drug: alpha-tocopherolquinone (A0001)
28 days of high dose (1.5 g total daily dose) oral A0001 capsules. Treatment
taken twice daily with meals.
Placebo: Placebo Comparator
Placebo Drug: placebo
28 days of placebo oral capsules. Treatment taken twice daily with meals.
Eligibility
Ages Eligible for Study: 18 Years to 60 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
•Individuals with genetically confirmed Friedreich's Ataxia (GAA or point
mutation)
•Impaired Glucose Tolerance, measured by Oral GTT
Exclusion Criteria:
•Overt Diabetes Mellitus
•Presence of clinically significant cardiovascular disease
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01035671
Contacts
Contact: Karlla W. Brigatti, MS (267) 426-9608
brigatti@email.chop.edu
Contact: Baali Muganga, BA (267) 426-9738
mugangab@email.chop.edu
Locations
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: David Lynch, MD, PhD
Sponsors and Collaborators
Penwest Pharmaceuticals Co.
Investigators
Principal Investigator: David Lynch, MD, PhD Children's Hospital of
Philadelphia
More Information
No publications provided
Responsible Party: Penwest Pharmaceuticals Co. ( Thomas Sciascia, MD/Chief
Medical Officer and VP Clinical Operations and Regulatory Affairs )
Study ID Numbers: FRD02
Study First Received: December 17, 2009
Last Updated: December 18, 2009
Hum Mol Genet. 2009 Dec 15;18(24):4843-52.
Epub 2009 Sep 25.
http://www.ncbi.nlm.nih.gov/pubmed/19783548?dopt=Abstract
Preventing Ataxin-3 protein cleavage mitigates degeneration in a Drosophila
model of SCA3.
Jung J, Xu K, Lessing D, Bonini NM.
Department of Biology and University of Pennsylvania, Philadelphila, PA
19104-6018, USA.
Protein cleavage is a common feature in human neurodegenerative disease.
Ataxin-3 protein with an expanded polyglutamine (polyQ) repeat causes
spinocerebellar ataxia type-3 (SCA3), also called Machado-Joseph disease,
and is cleaved in mammalian cells, transgenic mice and SCA3 patient brain
tissue. However, the pathological significance of Ataxin-3 cleavage has not
been carefully examined. To gain insight into the significance of Ataxin-3
cleavage, we developed a Drosophila SL2 cell-based model as well as
transgenic fly models. Our data indicate that Ataxin-3 protein cleavage is
conserved in the fly and may be caspase-dependent as reported previously.
Importantly, comparison of flies expressing either wild-type or caspase-site
mutant proteins indicates that Ataxin-3 cleavage enhances neuronal loss in
vivo. This genetic in vivo confirmation of the pathological role of Ataxin-3
cleavage indicates that therapies targeting Ataxin-3 cleavage might slow
disease progression in SCA3 patients.
http://www.ncbi.nlm.nih.gov/pubmed/20017723?dopt=Abstract
Coenzyme q10 in neuromuscular and neurodegenerative disorders.
Mancuso M, Orsucci D, Volpi L, Calsolaro V, Siciliano G.
Department of Neuroscience, Neurological Clinic, University of Pisa, Italy,
Via Roma 67, 56126 Pisa, Italy. mmancuso@inwind.it.
Coenzyme Q10 (CoQ10, or ubiquinone) is an electron carrier of the
mitochondrial respiratory chain (electron transport chain) with antioxidant
properties. In view of the involvement of CoQ10 in oxidative phosphorylation
and cellular antioxidant protection a deficiency in this quinone would be
expected to contribute to disease pathophysiology by causing a failure in
energy metabolism and antioxidant status. Indeed, a deficit in CoQ10 status
has been determined in a number of neuromuscular and neurodegenerative
disorders. Primary disorders of CoQ10 biosynthesis are potentially treatable
conditions and therefore a high degree of clinical awareness about this
condition is essential. A secondary loss of CoQ10 status following HMG-Coa
reductase inhibitor (statins) treatment has be implicated in the
pathophysiology of the myotoxicity associated with this pharmacotherapy.
CoQ10 and its analogue, idebenone, have been widely used in the treatment of
neurodegenerative and neuromuscular disorders. These compounds could
potentially play a role in the treatment of mitochondrial disorders,
Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis,
Friedreich's ataxia, and other conditions which have been linked to
mitochondrial dysfunction. This article reviews the physiological roles of
CoQ10, as well as the rationale and the role in clinical practice of CoQ10
supplementation in different neurological and muscular diseases, from
primary CoQ10 deficiency to neurodegenerative disorders. We also briefly
report a case of the myopathic form of CoQ10 deficiency.
http://www.news-medical.net/news/20091216/University-of-Florida-obtains-stimulus-grant-to-establish-ataxia-consortium.aspx
University of Florida obtains
stimulus grant to establish ataxia consortium
16. diciembre 2009 01:24
When treating devastating brain diseases such as Alzheimer's and Parkinson's,
doctors can reach into their medical bags to find something to help a
patient.
But they come up empty-handed when they try to help the vast majority of
patients with ataxia - disabling disorders that rob people of their balance
and coordination.
University of Florida neurologists are trying to change that with the help
of a $1 million Challenge grant from the National Institute of Neurological
Disorders and Stroke to establish a nationwide network of physician-scientists
with expertise in clinical ataxia research.
"A lot of times I explain to patients the symptoms of ataxia are similar to
what happens when someone gets too much alcohol into their system," says S.H.
Subramony, M.D., a professor of neurology in the UF College of Medicine. "In
either case there is slurred speech, inability to walk straight, falling,
blurry vision - symptoms that indicate damage to a part of the brain called
the cerebellum."
Ataxia - from the Greek "a taxis," meaning without order or coordination -
can leave a patient unable to coordinate their eye blinks, let alone move.
It can be hereditary or it could be brought on by strokes, tumors or other
medical problems. One form, called sporadic ataxia, appears without apparent
explanation in adults with no family history of the disease.
"Our first goal is to find a treatment to make patients' lives easier," said
Tetsuo Ashizawa, M.D., chairman of the UF department of neurology and
principal investigator and leader of the national effort, called the
Clinical Research Consortium for Spinocerebellar Ataxias. "But the common
thread ataxia shares with diseases such as Alzheimer's, Parkinson's,
Huntington's and ALS is that neurons are dying. By studying ataxia, we can
create insight into the neurodegenerative process in all of those diseases."
With laboratory and clinical research expertise from Ashizawa, Subramony and
Michael Waters, M.D., Ph.D., director of the neurology department's stroke
program, UF will lead nine other consortium institutions, including the
Johns Hopkins University and Harvard University. The institutions are
strategically placed across the nation so patients who have difficulty
traveling can find close and state-of-the-art health care.
The ataxia consortium is part of the NIH's Rare Diseases Clinical Research
Network, which will be awarding more than $117 million over the next five
years to explore the natural history, epidemiology, diagnosis and treatment
of more than 95 rare diseases.
By definition, a rare disease affects fewer than 200,000 persons in the
United States. But put them all together - 6,500 rare diseases have been
identified - and an estimated 25 million Americans are affected. Diabetes,
in comparison, affects an estimated 24 million people.
"Collectively rare diseases can become very huge public health problem even
though the reach of each individual disease is small," Ashizawa said. "I
think the NIH recognized the need to provide outreach and medical care to
patients, in addition to the need for research. Now we have a huge
responsibility to achieve our goals for the taxpayers."
UF researchers will be working with cell cultures, animal models and patient
samples to find targets to alleviate ataxia problems. In the meantime,
scientists will build a natural history database to bring this devastating
disease into more precise focus.
"We want to know how a patient will progress from day to day and hour to
hour if they have degenerative ataxia disorders," Ashizawa said. "We want to
know what factors worsen or improve the condition. For example, when
patients are calm, they seem to do better. When they're upset and rushed,
they do terribly. If they drink alcohol, they are much worse."
Creating or finding a drug that would help these patients is one of the
consortium's goals. Ashizawa notes that it may be possible that deep brain
stimulation surgery, a technique UF has expertise in that uses tiny
electrical pulses to influence movement or moods, may be beneficial.
The first step is to identify the patients and create a nationwide registry
funded by the NIH and the National Ataxia Foundation. In addition, the
consortium is collaborating with ataxia groups in Europe, South America and
Japan.
"Collaboration is a critical element of rare diseases research and the
partnerships represented in this program have tremendous potential to make
great strides in understanding these diseases," according to a statement by
Stephen C. Groft, Pharm.D., director of NIH's Office of Rare Diseases
Research. "The network emphasizes collaboration not just among investigators
from multiple research sites but between investigators and patient advocates
as well."
Challenge grants are part of the American Recovery and Reinvestment
Initiative and address specific scientific and health research challenges
that will benefit from two-year jumpstart funds.
Source: University of Florida
GLUTEN ATAXIA
http://celiacnurse.com/neurological-symptoms-ataxia-neuropathies-seizures-strokes-migraines-myopathies-dementia-associated-with-undiagnosed-celiac-disease-gluten-intolerance-or-sensitivities/
http://www.ncbi.nlm.nih.gov/pubmed/19936278?dopt=AbstractPlus&holding=f1000,f1000m,isrctn
Metal chelators coupled with nanoparticles as potential therapeutic agents
for Alzheimer's disease.
Liu G, Men P, Perry G, Smith MA.
Department of Radiology, University of Utah, Salt Lake City, UT 84108, USA.
Alzheimer's disease (AD) is a devastating neuro-degenerative disorder
characterized by the progressive and irreversible loss of memory followed by
complete dementia. Despite the disease's high prevalence and great economic
and social burden, an explicative etiology or viable cure is not available.
Great effort has been made to better understand the disease's pathogenesis,
and to develop more effective therapeutic agents. However, success is
greatly hampered by the presence of the blood-brain barrier that limits a
large number of potential therapeutics from entering the brain. Nanoparticle-mediated
drug delivery is one of the few valuable tools for overcoming this
impediment and its application as a potential AD treatment shows promise. In
this review, the current studies on nanoparticle delivery of chelation
agents as possible therapeutics for AD are discussed because several metals
are found excessive in the AD brain and may play a role in the disease
development. Specifically, a novel approach involving transport of iron
chelation agents into and out of the brain by nanoparticles is highlighted.
This approach may provide a safer and more effective means of simultaneously
reducing several toxic metals in the AD brain. It may also provide insights
into the mechanisms of AD pathophysiology, and prove useful in treating
other iron-associated neurodegenerative diseases such as Friedreich's
ataxia, Parkinson's disease, Huntington's disease and Hallervorden-Spatz
Syndrome. It is important to note that the use of nanoparticle-mediated
transport to facilitate toxicant excretion from diseased sites in the body
may advance nanoparticle technology, which is currently focused on targeted
drug delivery for disease prevention and treatment. The application of
nanoparticle-mediated drug transport in the treatment of AD is at its very
early stages of development and, therefore, more studies are warranted. |
