Compounds, Methods, and Treatments for Abnormal Signaling Pathways for Prenatal and Postnatal Development

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

[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 formation during gestation. Still further, the...

AI Technical Summary

Benefits of technology

The technical effect of this patent is to provide a method to prevent or reduce the rate of birth defects.

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 Folbp1 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).

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