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Recent Patents on Endocrine Metabolic
& Immune Drug Discovery
ISSN: 1872-2148
Recent Patents on Endocrine,
Metabolic & Immune Drug Discovery
Volume 4, Number 2, June 2010
Contents
Serum Amyloid A and Its Potential Physiological / Pathological
Functions - An Overview of Patents Pp.
89-99
Katja Lakota, Katjusa Mrak-Poljsak, Blaz Rozman and
Snezna Sodin-Semrl
[Abstract] [Purchase
Article]
B Lymphocytes, Potent Antigen Presenting
Cells for Preferential Expansion of Allo - Reactive FoxP3+
CD4 Regulatory T Cells Pp. 100-110
Xinjian Chen
[Abstract] [Purchase
Article]
Recent Patents in Diagnosis and Treatment
for Inborn Errors of Metabolism Pp. 111-130
Ángela J. Espejo, Luis F. Malaver, Alexander Rodriguez,
Rocío del P. Cuaspa, Carlos J. Alméciga-Diaz
and Luis A. Barrera
[Abstract] [Purchase
Article]
Dolichol: A Natural Biomarker of Aging Endowed
With a Photoenhanced ghly-Effective Solar Filter Activity
Pp. 131-137
Ranieri Bizzarri and Ettore Bergamini
[Abstract] [Purchase
Article]
Asymptomatic Primary Hyperparathyroidism: Management
and Implications Pp. 138-145
Malgorzata Trofimiuk, Dorota Pach and Alicja
Hubalewska Dydejczyk
[Abstract] [Purchase
Article]
Recent Advances in the Development of
Novel Therapeutics Targeting Dendritic Cells Pp.
146-152
Adriana J. Michielsen, Jacintha N. O’Sullivan and
Elizabeth J. Ryan
[Abstract] [Purchase
Article]
HDL - Cholesterol: The New Target for
Treatment Pp. 153-160
Sanjay Kalra, Bharti Kalra, Navneet Agrawal and
Ashraf Ganie
[Abstract] [Purchase
Article]
Protein Modification by β-N-Acetyl
Glucosamine (O-GlcNAc) in Insulin Signaling and Insulin
Resistance Pp. 161-171
Sudharsana R. Ande and Suresh Mishra
[Abstract] [Purchase
Article]
Patent
Selections Pp. 172-174
Abstracts
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Serum Amyloid A and Its Potential Physiological/Pathological
Functions - An Overview of Patents
Katja Lakota, Katjusa Mrak-Poljsak, Blaz Rozman and
Snezna Sodin-Semrl
Serum amyloid A (SAA) and its protein family
are highly conserved acute phase proteins elevated to high
levels during acute inflammation. Among the many different
roles SAA plays, one of the major ones is believed to be the
regulation of mechanisms designed to fight injuries, heal
infections and bring about their resolution to homeostasis.
In the circulation, SAA is mainly associated with high density
lipoproteins, can influence cholesterol transport and has
been implicated in the pathogenesis of atherosclerosis, rheumatoid
arthritis, and cancer. The deposition of SAA cleavage products
can lead to amyloidosis. So, patents describing possible modifications
of SAA pathophysiological role/s are relevant. SAA is one
of the highest positively responsive acute phase proteins
in humans, as well as in animals, and its levels have been
used to monitor diseases, treatment strategies and predict
outcomes. The major aims of this overview were to determine
the potential for SAA as a diagnostic tool (in terms of SAA
secretion as a cause or consequence of disease) and to critically
analyse patents proposing SAA measurement methodologies, in
order to determine the most optimal. A compilement of SAA
patents predominantly generated within the past decade will
also enable a better understanding of SAA, its genetics, the
expression of its isoforms, associations with other proteins,
especially its receptors, which could be important in diagnosis
and/or treatment of chronic inflammatory diseases.
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B Lymphocytes, Potent Antigen Presenting
Cells for Preferential Expansion of Allo - Reactive FoxP3+
CD4 Regulatory T Cells
Xinjian Chen
The naturally arising FoxP3+
CD4 T (nTr) cells are absolutely required for the induction
and maintenance of immunological tolerance to self antigens.
In addition to their physiological role, nTr cells can also
be utilized effectively for treatment of autoimmune diseases,
allograft rejection and graft versus host disease in animal
models. Due to the very low frequency in the peripheral blood,
nTr cells need to be expanded in ex vivo to generate
sufficient numbers for therapeutic applications. The nTr cells
can be expanded either polyclonally using anti-CD3/CD28 antibodies,
or in an alloantigen-specific manner using allogeneic antigen
presenting cells. The allospecific nTr cells are more therapeutically
effective with less risk to cause non-specific immune suppression
as compared to polyclonal nTr cells. Despite the success in
expanding murine nTr cells, little success has been achieved
in expanding human allospecific nTr cells, posing a major
barrier to the development of nTr cell-based immunotherapy
in humans. We have found that mouse B cells preferentially
activate and induce expansion of nTr cells in allogeneic mixed
lymphocyte reactions. The preferential expansion of Foxp3+
T cells can be further enhanced by a partial blockade of class
II MHC-TCR interaction, suggesting that nTr cells preferentially
respond to weak TCR stimulation. Extending the findings with
murine B cells, we have further found that human B cells can
efficiently expand allogeneic human nTr cells ex vivo.
The expanded nTr cells express very high levels of FoxP3,
maintain an anergic phenotype, and are potent suppressor cells
capable of inhibiting the alloreactivity of third-party responder
T cells at very low nTr-to-T effector cell ratios in an alloantigen-specific
manner. The allospecificity possessed by the B cell-expanded
nTr cells is not determined by the HLA haplotypes of the nTr
cells, but it is induced and determined by the HLA haplotype
of the B cells used to expand nTr cells. Our findings represent
a significant advance in the development of nTr cell-based
immunotherapy in humans and raise the possibility of using
“off-the-shelf” third-party nTr cells for therapeutic
applications. This review also outlines some patents on immunotherapy.
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Recent Patents in Diagnosis and Treatment
for Inborn Errors of Metabolism
Ángela J. Espejo, Luis F. Malaver, Alexander Rodriguez,
Rocío del P. Cuaspa, Carlos J. Alméciga-Diaz
and Luis A. Barrera
Inborn errors of metabolism (IEM) is a group of around
500 diseases, characterized by function alteration in proteins
or enzymes involving the intermediary metabolism of carbohydrates,
amino acids, and lipids, among others. Since their discovery
at the beginning of the last century, IEM have made important
contributions to different fields of biochemistry and medicine.
In this paper, a review of the recent patents for the diagnosis
and treatment of IEM will be presented. During the last years
significant achievements have been done for their diagnosis,
including the use of tandem mass spectrometry for the identification
of an important number of disorders and the use of genetic
and immunological techniques, which have allowed the development
of reliable diagnosis tests. Also, important progresses has
been done in therapeutic strategies, most of them based on
the use of recombinant DNA technology, such as enzyme and
gene therapies, and the use of small molecules for chaperone
and substrate reduction therapies. Improvements in classical
treatments, like nutritional management, have also contributed
in the generation of new therapeutic strategies for these
patients.
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Dolichol: A Natural Biomarker of Aging Endowed
With a Photoenhanced ghly-Effective Solar Filter Activity
Ranieri Bizzarri and Ettore Bergamini
Dolichol is a polysoprenoid lipid ubiquitous in eukaryotic
cell membranes. Its molecular structure comprises a sequence
of E and Z unsatured isoprene units tethered by a satured
isoprene unit bearing a hydroxyl group. Dolichol is mostly
present in the native form or esterified by lipid acids, and
it is thought to locate in the innermost part of the membrane
double layer, intertwining with the hydrophobic terminus of
the phospholipids. In spite of this peculiar arrangement,
no clear biological function of dolichol has been evidenced
yet, although a minor dolichyl phosphate pool is known to
assist the N-glycosylation of proteins in the endoplasmic
reticulum. Dolichol was recently found to strongly interact
with free-radicals, leading to a fast molecular disruption
without peroxidized by-products. This scavenging property
may explain why dolichol accumulates with age, representing
an excellent biomarker of the ageing process also sensitive
to ageing-preventing dietary regimes in living animals. Furthermore,
dolichol was shown to possess photoprotective characteristics
towards UV radiation. On account of its high biocompatibility,
its free-radical scavenging and photoprotective properties,
and its easy preparation from vegetable extracts, dolichol
has been proposed as main components for dermatological and
cosmetic compositions. The scientific background and the related
patents are reviewed here.
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Asymptomatic Primary Hyperparathyroidism: Management
and Implications
Malgorzata Trofimiuk, Dorota Pach and Alicja
Hubalewska Dydejczyk
The asymptomatic primary hyperparathyroidism
(PHPT) is one of the most common endocrinopathies. Considering
relatively slow progression of the disease, the untreated
PHPT patients are still at risk of classical (particularly
osteoporosis) and non-classical (cardiovascular, neurocognitive
and psychosocial) complications. The careful evaluation of
subjects, including exclusion of the secondary hyperparathyroidism,
is necessary, as some of the patients are normocalcemic even
in the presence of the disease complications. There are no
established risk factors for developing symptomatic disease.
At the moment surgery, particularly minimally invasive procedures,
seems the most beneficial and cost-effective therapy for asymptomatic
PHPT. According to the 2008 International Workshop guidelines
at least part of the patients may be followed-up conservatively,
provided that they will be closely monitored for possible
progressive disease. Pharmacological approach seems to be
an option for such patients. The anti-resorptive therapies,
particularly biphosphonates, are effective in management of
PHPT-related osteoporosis. Calcimimetics are very promising
agents lowering calcium and PTH levels, however costs of the
treatment may limit their long-term use in asymptomatic PHPT.
Also adequate Vitamin D nutrition is essential for conservative
management of such patients. This article outlines different
methods and recent patents for the treatment of hyperparathyroidism.
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Recent Advances in the Development of
Novel Therapeutics Targeting Dendritic Cells
Adriana J. Michielsen, Jacintha N. O’Sullivan and
Elizabeth J. Ryan
Dendritic cells (DCs) are a vital component
of the immune system. Their main function is to detect the
presence of pathogens and act as antigen presenting cells,
processing antigenic material then presenting it on their
surface in the context of major histocompatibility complex
(MHC) molecules to lymphocytes. Thus DCs provide a crucial
link between innate and adaptive immunity. DCs efficiently
activate naïve T cells making it particularly important
that they are correctly targeted by vaccines in order to induce
both effector and memory responses. This property of DCs has
important clinical application in the development of cancer
vaccines. However, under certain circumstances DCs can also
tolerize T cells, exploiting this may lead to the development
of novel therapies for T-cell mediated autoimmune diseases.
Recently, there has been substantial progress in the understanding
of how to manipulate DCs, however the challenge of translating
this from experimental models into the clinic remains. Some
patents on DCs, which may lead to the development of effective
immunotherapy, are discussed in this review.
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HDL - Cholesterol: The New Target for
Treatment
Sanjay Kalra, Bharti Kalra, Navneet Agrawal and
Ashraf Ganie
In spite of optimal treatment of LDL - cholesterol, as
per evidence -based guidelines, only a one third reduction
in cardiovascular risk is achieved in our patients. This has
led to the realization that other types of cholesterol, too,
need to be treated, in order to achieve ideal cardiovascular
health. The review focuses on high density lipoprotein (HDL)
cholesterol as a target for treatment, its importance, relevant
patents and current as well as future treatments.
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Protein Modification by β-N-Acetyl
Glucosamine (O-GlcNAc) in Insulin Signaling and Insulin
Resistance
Sudharsana R. Ande and Suresh Mishra
An enzymatic posttranslational modification of proteins
at serine or threonine residue by β-N-acetyl
glucosamine (GlcNAcylation, also known as O-GlcNAc
modification), a product of hexosamine biosynthetic pathway
(HBP), has been emerging as a fundamental regulatory mechanism
like protein phosphorylation. A significant surge in the information
in recent years due to technological advancement has implicated
an important role for GlcNAcylation in a wide variety of cellular
processes including cell division, metabolism, signal transduction
and transcription. Furthermore, GlcNAcylation in proteins
has been found to be intimately associated with phosphorylation
which is one of the most diverse regulatory mechanisms in
the biological system. Therefore, it is likely that altered
protein GlcNAcylation may underlie etiology of various diseases
including type 2 diabetes. Emerging evidence strongly indicates
a role for GlcNAcylation in the development of insulin resistance,
a hallmark of type 2 diabetes. Recent findings on protein
GlcNAcylation, especially in relation to insulin signaling
and insulin resistance have regenerated an immense interest
in this field; which was first reported in early nineties.
Here we summarize recent development in this area along with
unanswered questions and future direction at the end. Some
of the recently patented technologies in relation to GlcNAcylation
are also summarized in this review. Further investigations
in this area are timely and of critical importance with continuous
increase in the incidence of type 2 diabetes and diabetes
associated complications worldwide. A better understanding
of the underlying mechanisms may provide new opportunities
for the prevention and treatment of type 2 diabetes.
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