Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development

a signaling pathway and prenatal technology, applied in the field of inositol stereoisomers and derivatives thereof, can solve the problems of innocuous defects, adverse effects of impairment of folbpl gene function on the expression of several critical signaling molecules, and continuing medical problems of fetal malformations, so as to inhibit tumor survival factor and inhibit cancer growth

Inactive Publication Date: 2011-09-08
JENNINGS SPRING BARBARA BROOKE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0290]Yet it is another object of the invention to down regulate or inhibit Ap-1, thus inhibiting AP-1 transcription factor causes blockade of multiple signal transduction pathways and inhibits cancer growth.
[0291]It is another object of the invention to inhibit or downregulate ppRb thereby inhibiting tumor survival factor.

Problems solved by technology

Fetal malformations are a continuing medical problem in serious need of prevention and treatment.
These malformations can result in innocuous defects that pose no health or psychological issues, to those that pose primarily social or psychological issues (such as webbed digits, etc.), to those that pose medical issues of varying degrees of severity.
Impairment of the Folbpl gene function adversely impacts the expression of several critical signaling molecules.
However, some signaling cascade events can take days and many hours.
Disruptions of genes in one pathway can also have deleterious effects in other pathways and may result in serious dysmorphogensis or cancer years later.
Notwithstanding the above, there is still a tremendous amount that is still not fully understood in the art about the nature of the all the mechanisms involved in the etiology of these malformations and diseases and how to appropriately intervene to reduce or prevent the occurrence of such defects.
Fetal alcohol syndrome remains a significant psychosocial and clinical challenge.
While there have been great strides in preventing neural tube defects with folic acid, there are no known truly preventative strategies for preventing fetal alcohol syndrome related birth defects.
Unfortunately, cholesterol has a significant number of problems of its own that make it generally an unacceptable therapy for use in the human population and other treatment avenues are desired.
They do state however, that conclusions remain uncertain due to the lack of data about non-live births.
Even though interferon has been used widely for many years for the treatment of viral hepatitis, most of these patients respond poorly.
Unfortunately, folate supplementation still does not prevent all such cases, and presumably, the impairment of the Folbp1 due to aberrant sonic hedgehog signaling likely mediates the acquisition of folate resistance of the mother.
Myo-inositol was found not to be effective in this condition.
As stated above, scyllo-inositol actually resulted in an increase in fetal defects in non-diabetic pregnancies.
Phosphoinositide derangement and poor maternal metabolic turnover carries a relative risk in diabetic pregnancies for giving birth to a baby with lethal congenital anomalies like sirenomelia (Tahna, Davari et al, 2002).

Method used

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  • Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
  • Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
  • Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development

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example 1

[0646]In Jenkins, D. at al Anat 2007 Sep. 11, it states that studies of mouse mutants have demonstrated that Sonic hedgehog (SHH) signalling has a functional role in morphogenesis and differentiation at multiple sites within the forming urinary tract, and urinary tract malformations have been reported in humans with mutations that disrupt SHH signalling. However, there is only strikingly sparse and fragmentary information about the expression of SHH and associated signalling genes in normal human urinary tract development. (Jenkins, 2007) used immunohistochemistry to demonstrate that SHH protein was localised in distinct urinary tract epithelia in developing normal humans, in the urothelium of the nascent bladder and in kidney medullary collecting ducts. The expression patterns of the SHH-transducing proteins Patched (PTCH) and Smoothened (SMO) were consistent with long-range paracrine signalling associated with detrusor smooth muscle differentiation in the urogenital sinus. In the ...

example 2

[0648]Females determined to be at risk of fetal malformations and who are seeking a further pregnancy are split into no treatment, folate treatment, D-chiroinositol treatment, and Folate+D-chiroinositol treatment arms. The respective regimens are administered once daily from before conception through the end of the first trimester. Relative to the untreated controls, the frequency of fetal malformations is reduced in each of the non-control arms. However, the reduction in frequency of fetal malformations in the co-therapy of the present invention is significantly better than in either of the other treatment arms.

example 3

[0649]Females beginning birth control medication are assigned to similar treatment and control groups as in Example 1. Treatment is begun at the time of initiation of birth control medication, and continued until after a pregnancy occurs and for the following first trimester of pregnancy. Similar reductions as reported in Example 2 are seen. In addition, follow up of these females shows a lower level of breast cancer development than expected.

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Abstract

The present invention relates to prevention of congenital deformations. The invention further relates to cancer inhibition and prevention. The invention further relates to methods and compositions to modulate, antagonize, or agonize disparate signaling pathways that may converge to regulate patterning events and gene expression during prenatal development, post-natal development, and during development in the adult organism. The invention also relates to activators or deactivators of pyruvate kinase M2 (PKM2) for the treatment, prevention, or amelioration of diseases related to PKM2 function.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 12 / 387,239, filed Apr. 30, 2009; U.S. patent application Ser. No. 11 / 591,398, filed Nov. 1, 2006; and U.S. Ser. No. 12 / 001,869, filed Dec. 13, 2007, each of which is incorporated by reference in their entirety herein.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0002]Not ApplicableFIELD OF THE INVENTION[0003]The present invention relates to the field use of inositol stereoisomers and derivatives thereof, especially phosphorylated and carboxylated derivatives thereof (the invention compounds, some of which are novel compounds) in a wide range of disease states and medical conditions. The invention further relates to use of the invention compounds to modulate signaling pathways in the development and growth of various cells. Still further, the invention relates to reducing the incidence of fetal defects due to aberrant pattern formati...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/6615C07F9/06C07C69/96A61K31/265A61P35/00A61P3/04A61P3/10
CPCA61K31/265A61K31/6615C07F9/062C07F9/06C07D317/34C07C69/96A61K31/357A61P3/04A61P35/00A61P3/10Y02A50/30
Inventor JENNINGS-SPRING, BARBARA BROOKE
Owner JENNINGS SPRING BARBARA BROOKE
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