ENDECE Neural’s
NDC-1308 Induces Remyelination in Models of Multiple Sclerosis (MS)
NDC-1308 Induces Remyelination in Models of Multiple Sclerosis (MS)
Maturation of Myelin-producing Cells
Described in Presentation at CNS Diseases World Summit
Described in Presentation at CNS Diseases World Summit
Mequon,
Wisc., September 10, 2013 –
Scientists from ENDECE Neural presented preclinical data this week showing that
the company’s lead compound, NDC-1308, can address one of the root causes of
multiple sclerosis (MS) by inducing remyelination (restoration of the lost
myelin sheath in nerves that have been damaged by MS). The results, which were
presented at the CNS Diseases World Summit 2013 in Boston, suggest that
NDC-1308 can induce remyelination in an animal model of demyelination, in which
the neurotoxicant cuprizone was used to remove the myelin sheath from the axons
(nerve fibers) of mice.
Wisc., September 10, 2013 –
Scientists from ENDECE Neural presented preclinical data this week showing that
the company’s lead compound, NDC-1308, can address one of the root causes of
multiple sclerosis (MS) by inducing remyelination (restoration of the lost
myelin sheath in nerves that have been damaged by MS). The results, which were
presented at the CNS Diseases World Summit 2013 in Boston, suggest that
NDC-1308 can induce remyelination in an animal model of demyelination, in which
the neurotoxicant cuprizone was used to remove the myelin sheath from the axons
(nerve fibers) of mice.
According to
the researchers, NDC-1308 induces differentiation of oligodendrocyte progenitor
cells (OPCs) into mature oligodendrocytes (cells that synthesize and maintain
the myelin sheath that covers nerves in the brain and spinal cord). “For
decades, researchers have been seeking ways to induce remyelination in diseases
such as MS that are characterized by demyelination,” noted James G. Yarger,
Ph.D., chief executive officer and co-founder of ENDECE Neural. “Observations
that pregnant women typically do not experience the symptoms of MS during the
third trimester have led researchers to investigate various forms of synthetic
estrogen for the treatment of MS. Our research shows that the estradiol analog
NDC-1308 can induce remyelination in demyelinated axons in a cuprizone animal
model of demyelination.”
the researchers, NDC-1308 induces differentiation of oligodendrocyte progenitor
cells (OPCs) into mature oligodendrocytes (cells that synthesize and maintain
the myelin sheath that covers nerves in the brain and spinal cord). “For
decades, researchers have been seeking ways to induce remyelination in diseases
such as MS that are characterized by demyelination,” noted James G. Yarger,
Ph.D., chief executive officer and co-founder of ENDECE Neural. “Observations
that pregnant women typically do not experience the symptoms of MS during the
third trimester have led researchers to investigate various forms of synthetic
estrogen for the treatment of MS. Our research shows that the estradiol analog
NDC-1308 can induce remyelination in demyelinated axons in a cuprizone animal
model of demyelination.”
In their
poster presentation, Dr. Yarger and colleagues described how they synthesized
more than 40 proprietary estradiol analogs in which the core structure of
estradiol had been modified, and assessed how those modifications changed the
hormone’s biological activity. NDC-1308 was identified as the most potent of
several proprietary analogs having the ability to directly induce
differentiation of OPCs into mature oligodendrocytes. By contrast, the female
hormones estradiol and estriol do not exhibit that activity.NDC-1308 derives
its novel activity from the addition of an alkoxyalklyl moiety to the C-6
position on the estradiol B-ring. The investigators reported the following
findings:
poster presentation, Dr. Yarger and colleagues described how they synthesized
more than 40 proprietary estradiol analogs in which the core structure of
estradiol had been modified, and assessed how those modifications changed the
hormone’s biological activity. NDC-1308 was identified as the most potent of
several proprietary analogs having the ability to directly induce
differentiation of OPCs into mature oligodendrocytes. By contrast, the female
hormones estradiol and estriol do not exhibit that activity.NDC-1308 derives
its novel activity from the addition of an alkoxyalklyl moiety to the C-6
position on the estradiol B-ring. The investigators reported the following
findings:
·
In
a cuprizone mouse model of demyelination, a 2-week course of NDC-1308 (50 mg/Kg
once daily) was associated with a 20% increase in remyelination of hippocampal
regions of the brain (P<0.01) in proof-of-concept studies.
In
a cuprizone mouse model of demyelination, a 2-week course of NDC-1308 (50 mg/Kg
once daily) was associated with a 20% increase in remyelination of hippocampal
regions of the brain (P<0.01) in proof-of-concept studies.
·
Consistent
with the mouse cuprizone data, NDC-1308 enhanced remyelination in demyelinated
rat brain slices in culture visualized by staining for myelin basic protein.
Consistent
with the mouse cuprizone data, NDC-1308 enhanced remyelination in demyelinated
rat brain slices in culture visualized by staining for myelin basic protein.
·
NDC-1308
induced isolated OPCs to differentiate into mature oligodendrocytes in culture,
whereas estriol and estradiol did not (P<0.01).
NDC-1308
induced isolated OPCs to differentiate into mature oligodendrocytes in culture,
whereas estriol and estradiol did not (P<0.01).
·
NDC-1308
caused a dramatic upregulation of genes (5- to 75-fold) in signaling pathways
involved in OPC differentiation and myelin sheath production.
NDC-1308
caused a dramatic upregulation of genes (5- to 75-fold) in signaling pathways
involved in OPC differentiation and myelin sheath production.
“While
NDC-1308 is structurally similar to estradiol and estriol, it differs from
those two female hormones in that it potently promotes remyelination by
inducing OPC differentiation and maturation of oligodendrocytes at the sites of
demyelination,” explained co-investigator Bruce D. Trapp, Ph.D., who is chair
of the Department of Neurosciences at the Lerner Research Institute at the
Cleveland Clinic. “NDC-1308 induces significant remyelination of axons in the
demyelination model in mice.”
NDC-1308 is structurally similar to estradiol and estriol, it differs from
those two female hormones in that it potently promotes remyelination by
inducing OPC differentiation and maturation of oligodendrocytes at the sites of
demyelination,” explained co-investigator Bruce D. Trapp, Ph.D., who is chair
of the Department of Neurosciences at the Lerner Research Institute at the
Cleveland Clinic. “NDC-1308 induces significant remyelination of axons in the
demyelination model in mice.”
“There is a
large market opportunity for NDC-1308, as no commercially available drug is
capable of directly restoring the lost myelin sheath on damaged axons in
patients with MS,” added Dr. Yarger. “We envision NDC-1308 being administered
either alone or in combination with current therapeutics that target the immune
response and/or inflammation associated with MS. By inducing remyelination, it
may be possible to restore muscle control, mobility, and cognition in patients
with MS. Therefore, a drug that induces remyelination, such as NDC-1308, can
potentially double the size of the current market for MS therapeutics.”
large market opportunity for NDC-1308, as no commercially available drug is
capable of directly restoring the lost myelin sheath on damaged axons in
patients with MS,” added Dr. Yarger. “We envision NDC-1308 being administered
either alone or in combination with current therapeutics that target the immune
response and/or inflammation associated with MS. By inducing remyelination, it
may be possible to restore muscle control, mobility, and cognition in patients
with MS. Therefore, a drug that induces remyelination, such as NDC-1308, can
potentially double the size of the current market for MS therapeutics.”
About NDC-1308
NDC-1308 is a
novel chemical entity designed to address one of the root causes of MS, and is
being developed for potential use either alone or in combination with other MS
therapeutics that slow the progression of the disease. By controlling key genes
in pathways leading to myelin synthesis, NDC-1308 appears to induce restoration
of the lost myelin sheath that is believed to cause the devastating symptoms of
MS. NDC-1308 is a small molecule that readily crosses the blood-brain barrier,
allowing it to reach the tissues in the brain and spinal cord where promoting
myelin production is needed. ENDECE Neural discovered NDC-1308 in-house, and
owns the intellectual property surrounding the compound.
novel chemical entity designed to address one of the root causes of MS, and is
being developed for potential use either alone or in combination with other MS
therapeutics that slow the progression of the disease. By controlling key genes
in pathways leading to myelin synthesis, NDC-1308 appears to induce restoration
of the lost myelin sheath that is believed to cause the devastating symptoms of
MS. NDC-1308 is a small molecule that readily crosses the blood-brain barrier,
allowing it to reach the tissues in the brain and spinal cord where promoting
myelin production is needed. ENDECE Neural discovered NDC-1308 in-house, and
owns the intellectual property surrounding the compound.
About
ENDECE Neural
ENDECE Neural
ENDECE Neural
is a private biotechnology company at the forefront of developing therapies to
repair and potentially reverse damage caused by devastating neurological
diseases such as multiple sclerosis (MS). A wholly owned subsidiary of ENDECE
LLC, ENDECE Neural was founded in 2011 to focus on the development of what
could be the first drug capable of inducing remyelination of damaged nerves in
patients with MS. The company is leveraging decades of accumulated knowledge
about how activation of estrogen receptors in a specific manner affects gene
regulation. Researchers at ENDECE Neural have identified small-molecule
compounds that upregulate key genes in pathways involved in promoting myelin
synthesis. ENDECE Neural is developing NDC-1308, which appears to directly
induce OPCs to differentiate into mature oligodendrocytes that restore the
depleted myelin sheath in patients with MS. ENDECE Neural discovered and owns
the intellectual property surrounding its compounds, and the company’s
management team has an extensive track record of successfully taking products
from the laboratory through FDA approval and commercial release.
is a private biotechnology company at the forefront of developing therapies to
repair and potentially reverse damage caused by devastating neurological
diseases such as multiple sclerosis (MS). A wholly owned subsidiary of ENDECE
LLC, ENDECE Neural was founded in 2011 to focus on the development of what
could be the first drug capable of inducing remyelination of damaged nerves in
patients with MS. The company is leveraging decades of accumulated knowledge
about how activation of estrogen receptors in a specific manner affects gene
regulation. Researchers at ENDECE Neural have identified small-molecule
compounds that upregulate key genes in pathways involved in promoting myelin
synthesis. ENDECE Neural is developing NDC-1308, which appears to directly
induce OPCs to differentiate into mature oligodendrocytes that restore the
depleted myelin sheath in patients with MS. ENDECE Neural discovered and owns
the intellectual property surrounding its compounds, and the company’s
management team has an extensive track record of successfully taking products
from the laboratory through FDA approval and commercial release.
###
READ ANOTHER announcement of this article, by clicking here
.
Visit our MS Learning Channel on YouTube: http://www.youtube.com/msviewsandnews
