Epigenetic therapy

[1] Altered gene expression patterns can result from chemical modifications in DNA and chromatin, to changes in several regulatory mechanisms.

Several diseases, especially cancer, have been suspected of selectively turning genes on or off, thereby resulting in a capability for the tumorous tissues to escape the host's immune reaction.

Some of these drugs, including 5-azacytidine, Decitabine, and Zebularine, have been shown to reactivate the cellular anti-tumor systems repressed by cancer, enabling the body to weaken and kill off the tumor.

[17] Polyphenols, a type of phytochemical that can be found in everyday foods and ingredients like tea, apples, and various forms of berries, have been shown to have anticancer effects.

As of now, initial investigations have established links between DNA methylation, histone modifications, RNA-based mechanisms, and the onset of cardiovascular diseases such as atherosclerosis, cardiac hypertrophy, myocardial infarction, and heart failure.

Additionally, upregulation of a number of miRNAs has been shown to be associated with acute myocardial infarction, coronary artery disease, and heart failure.

Studies have shown that miRNAs can influence myocardial angiogenesis and the survival and proliferation of cardiomyocytes by regulating target gene expression.

LSD1 may play a major role in diabetic retinopathy through the downregulation of Sod2 in retinal vascular tissue, leading to oxidative damage in those cells.

The DNMT inhibitors 5-azacytidine and 5-aza-20-deoxycytidine have both been approved by the FDA for the treatment of other conditions, and studies have examined the effects of those compounds on diabetic retinopathy, where they seem to inhibit these methylation patterns with some success at reducing symptoms.

A number of preclinical studies have suggested that adding a treatment to metformin that would inhibit acetylation and methylation of DNA and histone complexes.

[34] While there are many causes for Autism spectrum disorder to manifest (viral infection, encephalitis, or an auto immune reaction,[34] but the primary reasons are genetic or epigenetic.

Maternal health during pregnancy, including taking folic acid, has been shown to affect the chances of not having ASD through epigenetic means.

While there are no current therapeutics approved for epigenetic use in autism there are a number of potential categories, histone deacetylase inhibitors (HDACis),[39] and DNA methyltransferases.

Valproic acid, commonly called Vorinostat, is an HDACi that helps with mood stabilization, this shows that it has potential for other neuro applications.

HDAC1 has a large impact on many functions in the body, including many neuro regions, this makes it a good candidate for a potential Autism therapy.

When the genes encoding BDNF and NMDA receptors experience increased acetylation, they become more "accessible" for transcription, the first step in protein production.

So, enhanced expression of BDNF and NMDA receptors seems to bolster neural plasticity, facilitating the brain's capacity to form new connections and adjust its responses to anxiety-provoking stimuli.

Research has shown that pharmacological manipulation of NMDA receptors can influence fear extinction learning and enhance the efficacy of exposure therapy.

For example, drugs that enhance NMDA receptor function, such as D-cycloserine, have been used as adjuncts to exposure therapy to facilitate fear extinction in individuals with anxiety disorders.

BDNF plays a pivotal role in fear extinction learning, crucial for exposure therapy, by facilitating synaptic plasticity and consolidating safety memories.

Targeting epigenetic modifications of BDNF presents a novel approach to modulating fear extinction processes, potentially improving exposure therapy outcomes.

Integrating genetic information, such as BDNF polymorphisms, with epigenetic profiles and clinical data allows for personalized treatment approaches.

Identifying individuals likely to benefit from targeted epigenetic interventions could enhance fear extinction learning and improve treatment outcomes in exposure therapy.

This interplay between BDNF, exposure therapy, and epigenetic regulation holds promise for optimizing treatment outcomes and advancing personalized medicine approaches for anxiety disorders.

Exposure therapy's effectiveness in rodents is increased by the administration of Vorinostat, Entinostat, TSA, sodium butyrate, and VPA, all known histone deacetylase inhibitors.

Rodent studies have indicated that administration of HDAC inhibitors without successful exposure therapy worsens anxiety disorders significantly,[46] although the mechanism for this trend is unknown.

An example of the growing evidence that indicates that successful psychotherapy can be linked to alterations in epigenetic markers, particularly DNA methylation, and could serve as a potential indicator of treatment efficacy is a research paper titled "Epigenetics of traumatic stress: The association of NR3C1 methylation and posttraumatic stress disorder symptom changes in response to narrative exposure therapy".

[47] This study explored the relationship between DNA methylation at the glucocorticoid receptor gene (NR3C1) and the success of psychotherapy in treating Posttraumatic Stress Disorder (PTSD) among conflict survivors in Northern Uganda.

These findings suggest that epigenetic changes at NR3C1 may play a role in the success of trauma-focused therapy, highlighting the importance of glucocorticoid signaling in PTSD treatment.

Research findings have demonstrated that schizophrenia is linked to numerous epigenetic alterations, including DNA methylation and histone modifications.