Journal of Genetic Syndrome & Gene Therapy

Having entered the genomics era with confidence in the future of medicine, including psychiatry, identifying the role of DNA and polymorphic associations with brain reward circuitry has led to a new understanding of all addictive behaviors. It is noteworthy that this strategy may provide treatment for the millions who are the victims of "Reward Deficiency Syndrome" (RDS) a genetic disorder of brain reward circuitry. This article will focus on drugs and food being mutuality addictive, and the role of dopamine genetics and function in addictions, including the interaction of the dopamine transporter, and sodium food...

Over time, based on evidence-based medicine, a number of hormonal test levels including IGF-1 had been raised or lowered to meet new criteria standards. In particular, IGF-1 plasma levels have been shown in several studies to be an independent diagnostic tool in Adult Growth Hormone Deficiency (AGHD). Many endocrinology studies link low IGF-1 plasma levels with low levels of other anterior pituitary hormones (i.e., LH, FSH, and TSH). Low IGF-1 is considered by most to be between 84-100 µ/l and numerous studies recommend that raising IGF-1 to high normal range reverses Chronic Medical Diseases (CMD), improves bone mineral density (BMD), and fibromyalgia...

The understanding that genes play a significant role in reward dependence and associated behavioral and drug addictions is highlighted in the emergence of Reward Deficiency Syndrome (RDS). Here we show two case reports that unequivocally indicate the definite commonality between food and drug addiction. These human cases not atypically raise the question as to how to treat these two seemingly diverse addictions. We suggest that research directed in an attempt to induce natural activation of dopaminergic reward circuitry as a form of common therapy may indeed be parsimonious...

Hemophilia A is a hereditary disorder caused by various mutations in factor VIII gene resulting in either a severe deficit or total lack of the corresponding activity. Recent success in gene therapy of a related disease, hemophilia B, gives new hope that similar success can be achieved for hemophilia A as well. To develop a gene therapy strategy for the latter, a variety of model systems are needed to evaluate molecular engineering of the factor VIII gene, vector delivery efficacy and safety-related issues...

BACKGROUND: Expression of Rab25, which is located in the 1q amplicon present at high frequency in many cancer lineages, promotes cancer cell survival under multiple stress conditions. While Rab proteins play essential roles in all stages of vesicle trafficking, the functions and endogenous cargoes for Rab25 remain to be fully elucidated. Osteoprotegerin (OPG) is a secreted glycoprotein that binds the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) thus preventing it from activating the TNF-family death receptors...

Müllerian and vaginal anomalies are congenital malformations of the female reproductive tract resulting from alterations in the normal developmental pathway of the uterus, cervix, fallopian tubes, and vagina. The most common of the Müllerian anomalies affect the uterus and may adversely impact reproductive outcomes highlighting the importance of gaining understanding of the genetic mechanisms that govern normal and abnormal development of the female reproductive tract. Modern molecular genetics with study of knock out animal models as well as several genetic syndromes featuring abnormalities of the female reproductive tract have identified candidate genes significant to this developmental pathway...

The National Cancer Institute (NCI) and the American Cancer Society (ACS) predict that 1,638,910 men and women will be diagnosed with cancer in the USA in 2012. Nearly 577,190 patients will die of cancer of all sites this year. Patients undergoing current systemic therapies will suffer multiple side effects from nausea to infertility. Potential parents, when diagnosed with cancer, will have to deposit oocytes or sperm prior to starting systemic radiation or chemo-therapy for the future genetic testing and in vitro fertilization, while trying to avoid risks of iatrogenic mutations in their germ cells...

Work from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)(™) found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. This editorial focuses on the neurogenetics of brain reward systems with particular reference to genes related to dopaminergic function...

No abstract text is available yet for this article.

Immunofluorescent imaging is a valuable tool for investigating the outcome of gene therapy within the transduced tissue. With a multi-labeling technique, it is possible to both characterize local expression of the transgene and to evaluate the severity of the adaptive immune response through cytotoxic T cell infiltration. It is critical that the experimental parameters are optimal in order to prevent misinterpretation of important pathological events. To optimize this staining protocol, murine liver and skeletal muscle was transduced using recombinant adeno-associated virus encoding human factor IX...

There is a need for understanding and treating post-traumatic stress disorder (PTSD), in soldiers returning to the United States of America after combat. Likewise, it would be beneficial to finding a way to reduce violence committed by soldiers, here and abroad, who are suspected of having post-traumatic stress disorder (PTSD). We hypothesize that even before combat, soldiers with a childhood background of violence (or with a familial susceptibility risk) would benefit from being genotyped for high-risk alleles...

Adverse, unfavourable life conditions, particularly during early life stages and infancy, can lead to epigenetic regulation of genes involved in stress-response, behavioral disinhibition, and cognitive-emotional systems. Over time, the ultimate final outcome can be expressed through behaviors bedeviled by problems with impulse control, such as eating disorders, alcoholism, and indiscriminate social behavior. While many reward gene polymorphisms are involved in impulsive behaviors, a polymorphism by itself may not translate to the development of a particular behavioral disorder unless it is impacted by epigenetic effects...

Hemophilia A represents the most common inheritable deficiency of the coagulation proteins. Current state-of- the-art treatment consists of frequent prophylactic infusions of plasma-derived or recombinant FVIII protein to maintain hemostasis, and has greatly increased life expectancy and quality of life for many hemophilia A patients. This treatment approach is, however, far from ideal, due to the need for lifelong intravenous infusions, the high treatment cost, and the fact that it is unavailable to a large percentage of the world's hemophiliacs...

Muscle-directed gene therapy for hemophilia is an attractive strategy for expression of therapeutic levels of clotting factor as evident from preclinical studies and an early phase clinical trial. Notably, local FIX expression by AAV-mediated direct intramuscular injection to skeletal muscle persists for years. Development of intravascular delivery of AAV vector approaches to skeletal muscle resulted in vector in widespread areas of the limb and increased expression of FIX in hemophilia B dogs. The use of FIX variants with improved biological activity may provide the opportunity to increase the efficacy of these approaches...

Mindful of the new evolutionary ideas related to an emerging scientific focus known as omics, we propose that spiritual, social, and political behaviors may be tied in part to inheritable reward gene polymorphisms, as has been demonstrated for the addictions. If so, analyses of gene polymorphisms may assist in predicting liberalism or conservatism in partisan attachments. For example, both drinking (alcohol) and obesity seem to cluster in large social networks and are influenced by friends having the same genotype, in particular the DRD2 A1 allele...

Hemophilia A and B are monogenic bleeding disorders resulting from loss of functional coagulation factors VIII or IX, respectively. Prophylactic treatment requires frequent intravenous injections of exogenous factor VIII (F.VIII) or factor IX (F.IX), due to the short half-life of both factors. Hemophilia patients are at risk of developing neutralizing antibodies to F.VIII (~25-30%) or F.IX (~2-4%), which require the use of expensive bypass agents and immune tolerance induction protocols. Viral vector mediated liver gene transfer of F...

Recombinant vectors based on a non-pathogenic human parvovirus, the adeno-associated virus (AAV), have gained attention as a potentially safe and useful alternative to the more commonly used retroviral and adenoviral vectors. AAV vectors are currently in use in Phase I/II clinical trials for gene therapy of a number of diseases such as cystic fibrosis, α-1 antitrypsin deficiency, muscular dystrophy, Batten's disease, and Parkinson's disease, and have shown efficacy in patients with Leber's congenital amaurosis, and hemophilia B...

Now after many years of successful bariatric (weight-loss) surgeries directed at the obesity epidemic clinicians are reporting that some patients are replacing compulsive overeating with newly acquired compulsive disorders such as alcoholism, gambling, drugs, and other addictions like compulsive shopping and exercise. This review article explores evidence from psychiatric genetic animal and human studies that link compulsive overeating and other compulsive disorders to explain the phenomenon of addiction transfer...

Both Clinical trials and pre-clinical experiments for hemophilia gene therapy showed that it is important to overcome potential immune responses against gene transfer vectors and/or transgene products to ensure the success of gene therapy. Recently various approaches have been investigated to prevent or modulate such responses. Gene transfer vectors have been specifically engineered and immunosuppressive regimens have been administered to avoid or manipulate the immune responses against the vectors. In order to prevent cytotoxic lymphocyte or antibody formation induced by transgene expression, novel approaches have been developed, including methods to manipulate antigen presentation, development of variant genes encoding less immunogenic proteins or gene transfer protocols to evade immune responses, as well as immunosuppressive strategies to target either T and/or B cell responses...

Current treatment of hemophilia A by intravenous infusion of factor VIII (fVIII) concentrates is very costly and has a potential adverse effect of developing inhibitors. Gene therapy, on the other hand, can potentially overcome these limitations associated with fVIII replacement therapy. Although hemophilia B gene therapy has achieved promising outcomes in human clinical trials, hemophilia A gene therapy lags far behind. Compared to factor IX, fVIII is a large protein which is difficult to express at sustaining therapeutic levels when delivered by either viral or non-viral vectors...