University of Cincinnati's Biological Sciences Technologies Available for Licensing

113087 - Breath Test for Glucose

doug.nienaber@uc.edu (Doug Nienaber) — Wed, 21 Feb 2018 00:00:00 GMT

Self-monitoring of blood glucose is an $8 billion industry worldwide. Current methods require a sample of blood, which is extracted via painful needle sticks that can lead to complications. Though acetone in the breath has long been known to correlate well with glucose in the blood, a breath test for glucose has yet to reach the market.

Anastasios Angelopoulos and Jonathan Bernstein, faculty members (engineering and medicine, respectively) at the University of Cincinnati have developed a patent pending device that signals the future of glucose sensing technology—a breath test for glucose. A patient will breathe into the device and, in seconds, receive an optical indication of blood glucose. Other breath-based approaches require more chemical transformations with additional steps.

100037 - Enhanced tPA Activity and Therapy

uhlje@ucmail.uc.edu (Jill Uhl) — Tue, 16 Jan 2018 00:00:00 GMT

Researchers at UC have developed methods for inhibiting lysis of coagulated blood and reducing risk of excessive lysis comprising administration of lysis-inhibiting amounts of apolipoprotein E4, and methods for inhibiting lysis of coagulated blood and reducing risk of excessive lysis comprising administration of a specific level of a lysis-inhibiting agent wherein the specific level is based on the apolipoprotein phenotype of an individual, are provided. Methods for enhancing lysis of coagulated blood by administration of an Apo E peptide fragment to blood containing a clot lysis agent are also provided.

112005 - Appetite Stimulating Proteins

uhlje@ucmail.uc.edu (Jill Uhl) — Wed, 05 Jul 2017 00:00:00 GMT

Dr. Glenn Millhauser and his lab at the University of California, Santa Cruz (UCSC) in collaboration with Dr. Stephen Benoit at the University of Cincinnati have discovered a group of proteins that will ultimately be of value in treating extreme cases of eating disorders such as anorexia or cachexia.

The agouti-related protein (AgRP) is produced in the brain and is a potent appetite stimulant. The normal 50 amino acid polypeptide is produced in the hypothalamus and binds with high affinity to the melanocortin 3 and 4 receptors (MC3R and MC4R). Along with alpha-melanocyte stimulating hormone (apha-MSH) and neuropeptide Y, AgRP plays a central role in the regulation of mammalian feeding and metabolism. From intracerebroventricular (ICV) injection studies, AgRP is well documented to enhance feeding for one to two days following a single injection, and is probably longer acting than any other known hormone or drug.

UCSC researchers have previously isolated the specific region of AgRP that is required to bind to the MC receptors. New studies show regions adjacent to those that make receptor contact are rich with positive charges, and while they do not influence receptor affinity, they’re critical for AgRP's long acting activity. UCSC researchers have now designed non-natural proteins where they’ve selectively enhanced certain charge characteristics and are able to greatly extend the time over which a single AgRP injection stimulates feeding. Normally, from ICV injections in rats, AgRP stimulates feeding over a 24 - 72 hour period, one to three days. UCSC researchers show that the newly designed protein stimulates feeding for six days. Moreover, the cumulative food intake stimulated by UCSC’s designed AgRP is approximately double that of control over the lifetime of the experiment. The animals increase their body weight by 15% in a one week period, compared to 5% in animals treated with wild type AgRP.

103036 - Bisbenzamidines for the Treatment of Pneumonia

uhlje@ucmail.uc.edu (Jill Uhl) — Wed, 05 Jul 2017 00:00:00 GMT

Pneumonia caused by Pneumocystis carinii (PcP) remains a major opportunistic infection associated with AIDS patients, even in the era of Highly Active Anti-Retroviral Therapy (HAART). In the previous 2 decades, patients with AIDS have been a primary target of PcP, the population in which it remains a leading opportunistic infection. Limited therapeutic choices and adverse reactions to the two standard treatments, trimethoprim-sulfamethoxazole (TMP-SMX) and pentamidine (Mei, Gurunathan et al., 1998), cause the clinical management of this infection to remain problematic. Moreover, side effects in almost half of AIDs patients required switching to a less effective therapy.
Despite the efforts of several in vitro and in vivo screening projects, no better treatment than TMP-SMX for PcP has been identified. Strategies to exploit the effective combination of dihydrofolate reductase inhibitor and DHPS inhibitor of the TMP-SMX combination, by substitution of each component (e.g. TMP-dapsone) have not resulted in any therapies with increased efficacy. More recently, mutations in Pneumocystis genes which are the targets of TMP-SMX, atovaquone and dapsone were similar to those conferring resistance in other organisms such as Plasmodium falciparum. Previous therapy with these agents had a strong correlation to presence of the mutation, suggesting a selective mechanism was operational. Moreover, a Pc genotype with double mutations in the DHPS gene replaced the wild type genotype (no mutations) as the predominant type in certain regions of the country (e.g. San Francisco) implying that again, a dominant selection was occurring and these organisms were being transmitted throughout the human population in these regions.
The limited repertoire, problems in tolerance, and potential emerging resistance make it necessary to identify new efficacious treatments for PcP. Drug screening and development for anti-PcP agents has taken advantage of available rodent models of PcP and short term in vitro systems. Recombinant proteins have been used in some biochemical assays when the Pc gene was cloned as in the case of dihydrofolate reductase, but this application has been rarely used due to the paucity of Pc gene sequences previously available. Researchers at UC and Xavier University of Louisiana have developed a series of novel compounds which may be useful for the treatment of viral infections, such as pneumonia and for instance, pneumonia caused by Pneumocystis carinii. In vitro evaluation of these compounds using a P. carinii ATP detection assay indicated that the bisbenzamidines of the present invention functioned as anti-P. carinii agents.

103020 - A Family of Therapeutic Delivery Systems

uhlje@ucmail.uc.edu (Jill Uhl) — Fri, 12 May 2017 00:00:00 GMT

The present invention is in the fields of molecular biology, biochemistry and pharmaceuticals. In general, the invention provides compositions for the cellular delivery of nucleic acids, polypeptides and/or molecular complexes comprising nucleic acids and polypeptides, and methods of making and using such compositions. The present invention provides a new class of non-viral transduction vectors that can be used for both in vivo and in vitro applications. This includes unique polycationic polymers that can associate with many suitable bioactive molecules, including proteins and other compounds that posses multiple cationic sites. The polymer can act as a delivery vehicle for the associated bioactive molecule, in vivo or in vitro, to the cells of interest for the bioactive molecule. In one embodiment, the present invention provides for a new series of polyamides for use as gene delivery agents. Also disclosed are methods of using the polymers to bind products, e.g., oligonucliotides, and facilitate cellular uptake. In one embodiment, the invention provides for the in vitro delivery of plasmid DNA into cells. The present also provides for the use of these polymers for the delivery of a nucleic acid is biologically active into a cell.
Advantages
The polymers are nontoxic and suitable for (highly efficacious ) drug delivery, efficient intracellular gene delivery, as well as delivery of DNA, RNA, SiRNA and oligonucleotides. One family of polymers is completely biodegradable, yielding glucose and an oligoamine monomer that is similar in chemical structure to that found in the body. The polymers are suitable for noncovalent attachment of targeting agents for cell-type specific delivery.
Areas of Application
Both the polymers and the oligonucleotide decoys have clinical applications, either separately or in combination (i.e., with the polymer delivering the decoys into cells). The polymers also have applications as reagents for in vivo and in vitro delivery of bioactive molecules. Favorable in vitro test results have been achieved in a variety of primary cell lines. The oligonucleotides, both separately and with the polymers as a delivery vehicle, are being studied for treatment of myocardial ischemia/reperfusion.

115088 - Collagen Scaffolds Printed in 3D with Microscale Features

doug.nienaber@uc.edu (Doug Nienaber) — Fri, 28 Apr 2017 00:00:00 GMT

Collagen is the preferred scaffold for regeneration of bone and other tissues. The global market for scaffold element technology is over $450 million and is expected to grow rapidly (13% CAGR).

Professor Vasile Nistor and his doctoral student, Alex Bell, working at the University of Cincinnati, have demonstrated, for the first time, the ability to print 3D structures with microscale features in collagen. This breakthrough allows for a closer recreation of the native cellular environment. The collagen is not chemically modified and the resultant structure is biocompatible.

In comparison to scaffolds made of bovine serum albumin (BSA) or other proteins, Dr. Nistor’s group creates structures that are of similar geometric resolution, while employing superior material—type I collagen is already inherently part of the native extracellular matrix and provides more realistic structural cues to cells.

110060 - A Novel Genetic Marker for Food Allergy

uhlje@ucmail.uc.edu (Jill Uhl) — Mon, 17 Apr 2017 00:00:00 GMT

University of Cincinnati researchers with Cincinnati Children’s Hospital Researchers have identified a novel genetic marker for food allergy. The V75 IL-4Ra / Q130 IL-13 / T-159CÆT CD14 allele combination is strongly associated with food allergy and is an important genetic marker to identify at-risk infants. In addition, the genetic markers may be useful in predicting the natural history of food allergy and aiding the management of this common condition. The researchers have determined that with each locus analyzed at the level of genotypes, the TT (CD14 -159 CÆT) genotype was significantly associated with food allergy. However, no significant allele frequency difference between food allergy patients and normal controls was observed at any of the six polymorphic sites when analyzed individually. Sequential multi-locus analyses revealed significant excess of 2-locus VV (I75V IL-4Ra) – QR (R130Q IL-13), and QR (R130Q IL-13) – TT (159 CÆT CD14) in food allergy patients compared to controls (p = 0.029 and 0.011, respectively). This was caused by a dramatic increase of individuals carrying the allele combination of V75 IL-4Ra / Q130 IL-13 / T- 159CÆT CD14 in patients with food allergy, compared to controls (p = 0.008). Furthermore, this allele combination was associated with the phenotype of eczema among food allergy patients (p=0.02). Peanuts (n = 63), milk (n = 41), and egg (n = 39) were the major foods causing food allergy in this study. Peanuts, milk, and egg each had specific genetic fingerprints, and therefore this technology may be applicable in diagnosing food allergies in the future.

113056 - Patient-Specific Total Hip Arthroplasty Guides

doug.nienaber@uc.edu (Doug Nienaber) — Wed, 12 Apr 2017 00:00:00 GMT

A cross-disciplinary team at the University of Cincinnati have developed a medical device and process to improve the outcomes from total hip arthroplasty ("THA").

THA or hip replacement surgery is a surgery done to remove a diseased hip joint and replace it with an artificial joint, or prosthesis. Approximately 300,000 total hip replacement surgeries are performed annually in the US and many fail due to malpositioning. Failure of a hip replacement leads to revision surgery. Revision surgery can be a major procedure that requires complex techniques and potentially has higher complication rate than the original replacement surgery. In addition, some patients are not medically able to tolerate such a long and difficult surgical procedure.

The UC team has developed a novel method to create a device to assist surgeons with THA. The device uses patient-specific anatomy to ensure proper positioning of the implant. We have collected data from a promising cadaver pilot study. Our device and procedure will reduce the likelihood of the need for revision surgery and should be applicable to any joint replacement surgery.

113009 - Unambiguous Anthrax Detection Assay

uhlje@ucmail.uc.edu (Jill Uhl) — Wed, 12 Apr 2017 00:00:00 GMT

Dr. Jagjit Yadav’s lab has developed novel chromosomal primers for use in a multiplex detection assay for anthrax (Bacillus anthracis). Unlike current detection assays available which focus on plasmids pX01, pX02, and non-specific chromosomal markers, this assay relies on highly specific chromosomal primers. Thereby avoiding the misidentification of closely related non-anthracis species and unneeded misdiagnosis.

Our assay has been verified to yield the expected amplification products & melting curves for B. anthracis. Further, no comparable or spurious amplification products from any of the 45 strains of the most closely related non-anthracis species (20 B. thuringiensis, 17 B. cereus and 8 B. mycoides) were produced in the detection assay. Therefore our primers are excellent for the unambiguous detection and identification of B. anthracis.

107014 - Novel Wound Healing Device

uhlje@ucmail.uc.edu (Jill Uhl) — Wed, 12 Apr 2017 00:00:00 GMT

A fistula is an abnormal connection or passageway between organs or vessels that normally do not connect. The Enterocutaneous (EC) fistula arises between the intestine and the skin surface and occurs most often as a complication after bowel surgery. Stool or other enteric substances pass through the fistula and pool up in a wound bed (such as may be present following surgery), thereby preventing wound healing. Such fistulas may also develop in the setting of malnutrition, cancer, and inflammatory disease. Closure of such fistulas requires intensive in-patient wound management and can take up to several months.
Physicians at the University of Cincinnati developed a novel wound separator coupled to an ostomy appliance that physically separates the fistula from the wound bed, such that any stool, or other enteric substances, that pass through the fistula are prevented from communicating with the wound bed. As a result, healing is promoted because enteric substances are diverted from the wound bed, reducing the breakdown of soft tissue, skin, etc., and lowering the incidence of infection. The wound separator was utilized on several patients as part of a patient care customization plan. While no data was collected as part of a research study, the opinion of the treating physicians was that the device dramatically reduced healing time and no adverse effects were noted.
Advantages: Faster wound healing, decreased hospitalization times, adaptable for use with commonly used wound healing devices.

098013 - Compounds to Treat Obesity

uhlje@ucmail.uc.edu (Jill Uhl) — Wed, 12 Apr 2017 00:00:00 GMT

Obesity is now considered as a global epidemic with over one billion people being overweight. About $33 billion is being spent each year in USA on weight reduction products. To date no satisfactory drug is available to control obesity. Therefore, millions of dollars are spent each year towards the development of new treatments to fight this epidemic.

Neuropeptide Y (NPY) is the most abundant peptide present in the mammalian brain. It has also been characterized as the most powerful orexigenic (stimulation of feeding) substance isolated to date. As described below, UC researcher, Ambikaipakan Balasubramaniam, has developed two groups of compounds based on NPY to control food intake, and are currently looking for partners for further development of these anti-obesity compounds.

Group 1 Compounds: It has recently been demonstrated that peripheral administration of PYY(3-36), a NPY Y2 receptor-preferring ligand, can reduce appetite and food intake in normal and fasted rodents, as well as in normal and obese humans (Nature 418:650-654; 2002, N Engl J Med 349:941-948; 2003). However, PYY(3-36) can also potently interact with other NPY receptors (Y4 & Y5), which excludes its use as an anti-obesity drug.

In this regard, we have developed highly selective and potent (Ki = 1 nM) Y2-receptor agonists based on PYY(22-36) sequence, and shown that they exhibit potent and prolong in vivo activities (J Med Chem 49:3420-3427; 2000; Dig Dis Sci. 44:643-648; 1999). In addition, we have also developed highly selective and potent (Ki = 1 nM) Y2 receptor agonists based on PYY(25-36), and determined they exhibit potent activities in in-vivo models. All these analogs based on PYY(22-36), PYY(25-36) and their deletion peptides have been patented (US Patents: 5,604,203 & 6,046,167). Moreover, selected PYY(22-36) & PYY(25-36) analogs have been determined to inhibit food intake in a mice model during peripheral administration 2, 4 or 24 h.

Group 2 Compounds: We have developed a series of lower molecular weight compounds (< 600) based on NPY, and have previously shown that these compounds could significantly attenuate the food intake in NPY-treated and fasted rats over 4-8 h during central administration. The composition and the use of these compounds have also been patented (US patents 6,013,633 & 6,235,718). Recently, we developed additional new compounds to facilitate entry into the brain, and have now determined that these compounds could significantly inhibit the food intake in rats over 8 h (bolus dose, ip). These compounds could therefore be developed into drugs to treat obesity.

The technology has the following advantages:

Lower molecular weight compounds- will be economical to develop into drugs.
Highly potent and selective- will be active at lower doses & little or no side effect expected.
Compounds are active peripherally- Could be easily administered.
Relatively stable- long acting.

110057 - Sinus Dilation Device

uhlje@ucmail.uc.edu (Jill Uhl) — Wed, 08 Mar 2017 00:00:00 GMT

Dr. Allen Seiden in collaboration with UC's Medical Device Innovation and Entrepreneurship Program have developed a device which allows a single hand to manually control expansion of a dilation balloon on a rigid curved shaft, while providing the option of simultaneous suction.

This device gives the operator the ability to deploy a dilating balloon mechanism by means of a specially designed pistol grip. The balloon is manually inflated in two stages as the first and second trigger are pulled. The locking mechanism allows the operator to overcome large forces of pressure. The device also includes a release button to deflate the balloon.

The balloon is attached to the distal end of the rigid shaft, just after an angulation in the shaft that improves access. The balloon is inflated by a small diameter tube in such a manner that expansion and suction can be achieved simultaneously. The suction function operates independently of the dilation and can be operated separately.

Advantages:

Single-handed dual-stage dilation balloon expansion
Dilation and suction function separately and simultaneously
Angled, rigid shaft improves sinus access

107093 - Novel Molecules for Shiga Toxin Detection

uhlje@ucmail.uc.edu (Jill Uhl) — Fri, 03 Mar 2017 00:00:00 GMT

Shiga toxin producing Escherichia coli (STEC), including E. coli O157:H7, are emerging pathogens of major importance. E. coli O157:H7 alone causes an estimated 70,000 cases of disease per year in the United States. Disease caused by E. coli O157:H7 is characterized by diarrhea, hemorrhagic colitis, and the potentially fatal complication, hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is a major virulence factor of E. coli O157:H7 and has been included as a Select Agent of Biothreat agent list.

The pathogenic potential of an E. coli isolate is dependent on the type of Shiga toxin it produces. There is an urgent need for diagnostic agents that can discriminate between Stx1 and the deadlier form, Stx2, for effective intervention and the prevention of future outbreaks. Furthermore, closely related variants of Stx2 also differ in pathogenic potential. Commercially available diagnostic tests for Shiga toxin distinguish between Shiga toxin variants based on antigenic differences, not pathogenic potential. Thus, a test that distinguishes between Shiga toxin variants based on pathogenic potential represents significant advancement in diagnostic and therapeutic value for affected patients.

Invention

Researchers at the University of Cincinnati have developed novel, glycoconjugate ligands which mimic the natural receptors and exhibit specific and differential binding toward Shiga toxin variants based on biological activity. These glycoconjugates can be used as robust, specific, high affinity ligands for the detection and possibly treatment of Shiga toxin mediated disease. Additionally, the methods used to make and screen these glycoconjugates represent a platform technology that can be applied to many other toxins, viruses and bacteria. A patent application has been filed that includes novel compositions, methods for making and methods for screening glycoconjugates.

Advantages

Glycoconjugates distinguish Shiga toxin variants based on biological activity, not antigenicity and unlike antibodies, glycoconjugates are insensitive to genetic drift.
Glycoconjugates can be used in several assay platforms including ELISA and sensor arrays.
Glycoconjugates have superior thermal and chemical stability compared to antibodies.
No cross reactivity or false positives are expected with this class of compounds.

116022 - Mouse Model for Angiosarcoma and Lymphangiosarcoma

melissa.baines@uc.edu (Melissa Baines) — Thu, 02 Jun 2016 00:00:00 GMT

Dr. Jun-Lin Guan and his lab have developed a research tool for modeling angiosarcoma and lymphangiosarcoma.

This research tool is a genetically-engineered mouse model, that replicates all the main features of human angiosarcoma and lymphangiosarcoma, including invasion and metastasis. A technique for isolating primary tumor cells from the mice has also been developed. The in vitro cell-based assays have been optimized to test tumor cell growth, apoptosis and kinase activities.

This model would be useful to those Researchers engaged in the care of patients with angiosarcoma and lymphangiosarcoma, and patients with other vascular tumors and vascular malformation.

The technology currently has the following advantages:

Only animal model that replicates all aspects of the human angiosarcoma.
High formation rate and rapid growth rate of the tumors
Ideal model for screening new compounds.

115103 - Laser-Activated, Drug-Delivering, Nanoparticle Bubbles

doug.nienaber@uc.edu (Doug Nienaber) — Fri, 11 Mar 2016 00:00:00 GMT

Cancer treatment is the largest segment of nanomedicine, accounting for 35% of the market and valued at $19 billion in 2013. Targeted attack of cancer cells, while minimizing harm to healthy cells, remains an elusive challenge.

Professor Yoonjee Park, in work begun at MIT and ongoing at the University of Cincinnati, has developed a nanoparticle drug-delivery bubble with superior stability, preventing harm to healthy cells unless activated initially by laser, and then by ultrasound. Her particles are relatively inexpensive and can deliver lipophilic or hydrophilic compounds. In addition to cancers, glaucoma is a potential application.

111098 - An Acoustic Jet Device for Sleep Apnea

doug.nienaber@uc.edu (Doug Nienaber) — Fri, 19 Feb 2016 00:00:00 GMT

Dr. Ephraim Gutmark and Dr. Siddarth Khosla have developed a device for the treatment of sleep apnea.

Approximately 15 million Americans have obstructive sleep apnea (OSA). Portions of the upper respiratory tract collapse in OSA patients resulting in the blockage of the airways and reduced blood oxygen levels. As blood oxygen levels drop, the patient awakens and gasps for air. This cycle is repeated many times during the night. Left untreated, OSA is associated with a significant increased risk of cardiovascular events including hypertension, stroke and heart attack. Obstructive sleep apnea has been associated with a high risk for motor vehicle accidents; OSA increases the risk of motor vehicle accidents and is thought to account for 15-20% of the 40-50,000 deaths and almost 4,000,000 emergency department visits annually. Continuous Positive Air Pressure, or CPAP is an effective and widely recognized therapy for sleep apnea but is often under prescribed by physicians and under-utilized by patients. The positive air pressure prevents the airways of the upper respiratory tract from collapsing, preventing the apneic event. CPAP is efficacious but is not well tolerated by patients. Studies show that somewhere between 46% and 83% of patients are not compliant with CPAP therapy and remove the CPAP early in the night or skip use altogether.

The Acoustic Jet Device (AJD), developed by a collaboration between Dr. Ephraim Gutmark of the School of Aerospace Systems and Dr. Siddarth Khosla of the Department of Otolaryngology, has the ability to solve many of the problematic issues associated with CPAP therapy without compromising the therapy's effectiveness. Our technology circumvents the need to provide the tight seals required of traditional CPAP because it does not rely on pressurizing the entire upper respiratory tract. Instead the AJD needs only to be directed towards the nostrils of the patient to give a desired effect. Additionally the AJD has relatively low energy requirements to achieve airflows sufficient for therapeutic efficacy. These low energy requirements enable the AJD product to be run on batteries. In combination with its size, the AJD would lead to un-heard of mobility for CPAP patients who are currently tied to bulky equipment plugged into the mains. The AJD also has the potential to be used to provide improved airflow for patients with diseased lungs or even as a portable ventilator.

The AJD has the following advantages over current CPAP therapies:

a tight fitting mask or nasal interface is not required;
patients can open their mouths during sleep;
minimal tubing and equipment allows for increased freedom in sleep positions and mobility
selective pressurization of the respiratory tract reduces abdominal bloating;
it is much smaller and cost significantly less than the current CPAP therapies.

106109 - G-Protein Coupled Receptor Kinase-5 Polymorphism

hansenmh@ucmail.uc.edu (Michael Hansen) — Thu, 09 Apr 2015 00:00:00 GMT

The present invention is directed to compositions and methods relating to a G-protein coupled receptor kinase-5 polymorphism. The methods include, for example: detecting enhanced desensitization of the beta adrenergic receptor signaling pathway in an individual, assessing partial protection against heart failure progression in an individual, and assessing an individual's response to beta-blocker therapy. The compositions include polynucleotides or fragments thereof of a nucleotide sequence encoding for a G-protein receptor kinase-5 molecule with a thymine at amino acid position 122 and oligonucleotide primers that hybridize thereto.

103007 - Compositions and Methods for Targeted Drug Delivery

doug.nienaber@uc.edu (Doug Nienaber) — Wed, 18 Jun 2014 00:00:00 GMT

The present invention relates to synthetic host-rotaxanes, and in particular to novel synthetic host-rotaxanes that engage in molecular recognition events with a guest molecule to yield a host-guest complex. The present invention includes methods and compositions for transporting agents and macromolecues across biological membranes.
Although recent advances in drug delivery methods have produced active peptide and protein-based drugs, the technology suffers from a lack of suitable delivery systems. Among the problems of existing delivery systems is poor absorption of peptides through cellular membranes. The host-rotaxane of the present inventions shows almost DMSO-like ability to penetrate a cell membrane and deliver desired constituents to a cell.

108017 - Personalized Medicine - A Test for Individualized Cardiovascular Disease Treatment Protocols Based on Beta-1 Adrenergic Receptor Haplotype

Kellen.Sensor@uc.edu (Kellen Sensor) — Wed, 16 May 2012 00:00:00 GMT

ß-adrenergic receptors (ß-AR's) a class of G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline (norepinephrine) and adrenaline (epinephrine). ß receptors have the subtypes ß1, ß2 and ß3. All three are linked to Gs proteins, which in turn are linked to adenylate cyclase. Agonist binding to these receptors therefore causes a rise in the intracellular concentration of the second messenger cAMP.

ß subtype1-adrenergic receptors (ß1-AR's) are expressed on a number of cell types, including cardiomyocytes, vascular smooth muscle, epithelium, renal juxtaglomerular, and adipocytes. These receptors are targets for agonists in the acute treatment of decompensated heart failure, while ß1-AR antagonists are utilized in the treatment of cardiovascular diseases such as chronic heart failure, ischemic heart disease, cardiac arrhythmias, and hypertension. However, the response to ß1-AR agonists or antagonists appears to be highly variable between individuals, which is not readily explained by clinical status or demographic characteristics. Furthermore, the inventor has previously shown that the expression of ß1-AR, and the responsiveness to stimulation, can differ substantially between healthy individuals. Such variability between individuals suggests that the receptor may be polymorphic in the population, giving rise to altered expression as well as altered physiologic or pharmacologic responsiveness.

Invention
Dr. Stephen Liggett at the University of Cincinnati has invented a method for determining whether a treatment protocol for a human patient who is suffering from heart failure, ischemic heart disease, cardiac arrhythmias, or hypertension would include the administration of a beta blocker. The method also involves identifying locations of any polymorphisms in the ß1-AR sequence from the patient's biological sample, assigning a haplotype to the ß1-AR sequence based on the locations identified, and determining whether the treatment protocol includes administration of a beta blocker to the patient based on the haplotype assigned.

The invention offers the following advantages:

the invention forms the basis of a test to determine the best treatment protocol for cardiovascular disease
treatment protocols can be potentially tailored around the patient's individual genotype. This could lead to savings in terms of both costs and time.
potentially lead to the avoidance of unnecessary side effects

106082 - Structure of human platelet glycoprotein VI: A novel target for anti-thrombotic agents

briggsln@ucmail.uc.edu (Lynn Briggs) — Mon, 12 Dec 2011 00:00:00 GMT

Dr. Andrew Herr and colleagues at the University of Cincinnati have developed a protocol for the expression, purification, and refolding of the collagen-binding domain of human GPVI. The crystal structure of this refolded GPVI domain was solved to 2.4 Å resolution. GPVI formed a back-to-back dimer in the crystal, consistent with several studies suggesting GPVI was dimeric on the platelet surface. These data also revealed an unusual groove on the surface of GPVI that computational docking programs and published mutagenesis studies strongly suggest is the collagen binding site. The orientation and dimensions of the collagen binding grooves on the two GPVI proteins within a dimer precisely match the geometry of the intact collagen fiber.
This technology – a refolding protocol capable of generating milligram quantities of pure GPVI and the coordinates of the atomic structure of GPVI – provides critical information for the design and development of GPVI inhibitors as new therapies for human disease

109074 - Radiation Shielding Device

geoffrey.pinski@uc.edu (Ellen Banks) — Mon, 05 Dec 2011 00:00:00 GMT

Dr. Costea has created a lightweight, radiation shielding device. Made of transparent leaded material, the device reduces the radiation exposure of the medical professionals to almost zero, without decreasing their range of motion, visual contact with patients or the capability of performing fine movements with their hands and fingers. The dual shields are placed on wheels which are positioned in a tripod shape, one set on the external side and two separate sets on the other.

The shields’ positioning, which is opposite to the radiation tube and the patient's chest, provides medical professionals the flexibility of either standing or sitting while conducting medical procedures. While offering maximum radiation protection to the medical professionals’ entire body, these shields are easy to construct at an economical cost.

The invention has the following advantages:

Eliminates radition exposure to medical professionals
Allows medical professionals to utlize full range of motion
Mobile and adjustable

104041 - Management of the Newborn Experience

pinskig@ucmail.uc.edu (Geoffrey Pinski) — Mon, 05 Dec 2011 00:00:00 GMT

The University of Cincinnati, lead by Ms. Barbara Gilman RN, MSN, Ms. Shirley J. Adams, RN, MSN, Ms. Elizabeth E. Weiner RN, PhD, and Jeffery Q. Adams, MSCE, has developed a two hour interactive comprehensive program for educating nurses about the newborn experience.

The program is divided into four different modules, with a number of different sections:

Immediate Care of the Newborn
1. APGAR
2. Check for Anomalies
General Assessment: Appearance, Vital Signs & Measurements
1. Determine Heart Rate
2. Cord Care
Complete Assessment: Skin, Head, Chest & Abdomen
1. Identification of Fontanels
2. Abdominal Palpation
Complete Assessment: Genitalia, Extemities, Reflexes and Gestational Age
1. A circumcision
2. Ballard chart

104010 - Compounds to Treat Cardiovascular Ischemia and promote Wound Healing

Kellen.Sensor@uc.edu (Kellen Sensor) — Mon, 05 Dec 2011 00:00:00 GMT

Cardiovascular ischemia is a leading cause of illness and death in the United States. A number strategies including prevention through diet, exercise and lipid-lowering drugs, and medical intervention via angioplasty, stent placement and surgery are being used to alleviate the ischemic conditions. In addition, pro-angiogenesis compounds have also been used to enhance blood flow through collateral vessel formation. However, these treatments remain inadequate because of the complications associated with these strategies. Moreover, pro-angiogenesis factors, vascular endothelial cell growth factor (VEGF) and basic fibroblast growth factor (BFGF), used to enhance blood flow in ischemic tissues have also been associated with pathological angiogenesis and/or the proliferation of tumor cells. The latter observation warrants the development of novel compounds that would specifically promote angiogenesis in ischemic tissues.
Neuropeptide Y (NPY) is a 36-residue peptide amide originally isolated from porcine brain. It is abundantly present in the sympathetic nervous system surrounding the heart and blood vessels, and also present in endothelial cells and platelets. Recent investigations using rat hind limb ischemic model, mouse corneal micro-pocket assay and chicken embryonic chorioallantoic membrane assay have unequivocally shown that NPY exhibits a powerful angiogenisis effect. Moreover, NPY has also been shown to promote wound healing, a process dependent on angiogenesis. These actions of NPY are mediated by Y2 receptor subtypes because: 1) NPY did not exhibit angiogenic activities in Y2 receptor deficient mice; 2) [Leu31, Pro34]NPY, which does not bind to Y2 receptor, had no angiogenesis effect.
It is therefore clear that NPY Y2 receptor selective agonists will ultimately be used to treat cardiovascular ischemia and promote wound healing. In this regard, we have developed highly selective and potent (Ki = 1 nM) lower molecular weight Y2-receptor agonists based on PYY(22-36) and PYY(25-36) (US Patents: 5604203 & 6046167), and shown that they exhibit to potent and prolong in vivo activities (J Med Chem 49:3420-3427; 2000; Dig Dis Sci. 44:643-648; 1999). We are now looking for partners to develop these compounds as drugs to treat cardiovascular ischemia, Peripheral arterial disease (PAD), and to promote wound healing.
Advantages

Lower molecular weight compounds- will be economical to develop into drugs.
Highly potent and selective- will be active at lower doses & little or no side effect expected.
Relatively stable- long acting.

101033 - Method to Increase Milk Production

geoffrey.pinski@uc.edu (Ellen Banks) — Mon, 05 Dec 2011 00:00:00 GMT

Mammalian milk production is regulated by a feedback system in the mammary glands that results in reduced lactation when the frequency of milking is reduced. The baseline level of bovine milk production can be increased with a more frequent milking regimen, or with the administration of rBST (a recombinant bovine growth hormone) that counteracts this feedback response resulting in a boost in milk production by approximately 10 percent.

Dr. Nelson Horseman and colleagues have discovered a new method of regulating milk production exploiting a different mechanism which does not involve the use of hormones. The researchers have identified a key component of the feedback loop that regulates milk production in the mammary gland. They have found that this intrinsic feedback mechanism can be manipulated by the use of well-characterized pharmaceuticals either alone or in combination with certain biologically active substances.

Specifically, the researchers have found that the administration of various serotonin antagonists is effective in increasing milk production. This offers several advantages such as those listed below.

Advantages:

Potential lower manufacturing costs

Absence of any compounds in milk

Reduced consumer resistance due to lack of use of hormones

Can be developed for oral administration, suggesting ease of use

Compounds by themselves have very safe and well understood pharmacological profiles

100021 - Peptides with Antioxidant and Antimocrobial Properties

briggsln@ucmail.uc.edu (Lynn Briggs) — Mon, 05 Dec 2011 00:00:00 GMT

Research at UC has led to the development of methods of treating conditions associated with lipid oxidation or microbial proliferation which include the step of administering a composition comprising a pharmacologically effective amount of an antioxidant or antimicrobial lung surfactant protein compound. These peptides derived from lung surfactant protein compounds possess lipid oxidation inhibiting and/or antimicrobial properties.

105008 - Method of Killing Cancer Cells by Neurotransmitter Inhibition

geoffrey.pinski@uc.edu (Ellen Banks) — Thu, 31 Mar 2011 00:00:00 GMT

Breast cancer is a major contributor to cancer-related mortality. Standard of Care treatments for breast cancer are fraught with inadequacies related to chemotoxicity and many patients are left with few treatment options beyond radical tissue resection and traditional or experimental therapies.
Researchers at the University of Cincinnati have discovered a novel mechanism of triggering cell death in several human breast cancer cell lines. An apoptotic mechanism has been identified for one particular line, and additional experimental avenues are being pursued to further characterize the mechanisms involved in producing cytotoxicity.

104079 - Endovascular Aneurysm Neck Closure Device

Kellen.Sensor@uc.edu (Kellen Sensor) — Thu, 14 Jan 2010 00:00:00 GMT

Endovascular therapy of cerebral aneurysms by coil embolization is well accepted by the surgical community as a safe and efficiacious alternative to open surgical repair of aneurysms by traditional clip ligation methods. Coil embolization benefits the patient with reduced mortality and better short term morbidity in instances of vascular rupture and shorter hospital stays and recovery times for instances of unruptured aneurysms. Standard of Care methods involve occlusion of the anyeurysmal lumen with platinum microcoil devices. New liquid embolics are also being developed by researchers, but both suffer from high aneurysm recurrence rates due to compaction and recanalization of the defect. Open surgical repair has a much lower frequency of failure, but carries the burden of tradition surgical method risk. A new method of aneurismal occlusion that offered the durability of traditional methods, coupled with the more favorable risk profile of less invasive techniques would benefit the patient. A research physician at the University of Cincinnati has designed an intravascular device to address the need for a occlusive mechanism that achieves similar fusion and closure end points from tissue apposition and compression at the neck of the aneuryism compared with traditional open surgical approaches.

102042 - Potential Tumor Suppressor Gene

Kellen.Sensor@uc.edu (Kellen Sensor) — Thu, 14 Jan 2010 00:00:00 GMT

Lung cancer is the most common cause of cancer-related deaths in the United States, and in spite of the progress that has been made in understanding the molecular biology of the disease mortality rates have not decreased significantly. To a large extent this is due to the fact that lung tumors form metastases early when the primary tumor is small and less likely to be detected. What is needed are effective systemic therapies, and diagnostic tools to detect tumors at early, pre-metastatic stages. Chromosomal deletions in tumors are usually taken to indicate the location of one or several tumor suppressor genes in the same region. We have identified a gene with several splice variants close to a chromosomal region that has been shown to be homozygously deleted in lung tumors. The first exon of the gene contains an evolutionary conserved predicted phosphorylation site for PKB/Akt, a key mediator of signal transduction processes involved in cell proliferation and survival. Using a synthetic 13-aa peptide as a substrate for recombinant PKB/Akt we have confirmed that the predicted threonine is a putative phosphorylation site for PKB/Akt. PKB/Akt can both promote proliferation and inhibit apoptosis through phosphorylation of key proteins like p21, the forkhead transcription factor, BAD, and others. Often this leads to inhibition or sequestration of the phosphorylated protein. Several other proteins known to be involved in proliferation or apoptosis, such as DAP kinase, Huntington protein, and several caspases, although not yet shown to be PKB substrates contain putative PKB phosphorylation sites. The first six exons of the gene are ubiquitously expressed in all tissues and cell lines that we have screened. Alternative splicing of the first exon creates a transcript with shorter reading frame and a different protein product. In many cell lines and tissues the last internal exon is alternatively spliced onto exons downstream of the sixth exon to generate low expression levels of numerous alternative transcripts of which many are very long and some span the minimal region of homozygous deletion mentioned above. Preliminary results indicate that these variants are differentially expressed in tumors versus normal tissue.

The significance of the various splice variants of this gene is not clear yet, but preliminary experiments indicate that they are differentially expressed in normal tissue versus tumors. If changes in expression occur early in cancer development, this could facilitate early detection of cancer, and a diagnostic procedure or kit could be developed. The fact that there is a putative PKB/Akt phosphorylation site in the first exon of our gene raises the possibility that its various splice variants function in the PKB/Akt cell survival pathway, which is up-regulated in many types of cancer. It appears to be the major pathway for survival of cancer cells. Thus our gene could become targets for new therapeutic strategies for chemotherapy and chemoprevention. We have unpublished data showing that the PKB/Akt pathway is activated in many early lesions (hyperplasia and dysplasia).

102037 - Method for Determining Dietary Fat Absorption

Kellen.Sensor@uc.edu (Kellen Sensor) — Thu, 14 Jan 2010 00:00:00 GMT

The current invention is a composition used as a test meal comprising a predetermined amount of dietary fat and a predetermined amount of a non-absorbable fat marker, such as a sucrose polyester in the form of sucrose behenate. The method for measuring total dietary fat absorption by the digestive tract of a subject comprises the steps of administering ingestion of the test meal by the subject, collecting a sample of fecal matter at an interval following ingestion of the test meal, measuring the amount of the of non-absorbable fat marker recovered in the fecal sample and calculating the amount of dietary fat recovered from the test meal to determine the amount of dietary fat that was absorbed by the digestive tract of the subject. The methods of the invention can be used to diagnose malabsorption of dietary fat by the digestive tract of a subject or impairment of dietary fat digestion. The advantage of this current invention over existing tests is that patients may take only one test and only a single “marked” stool sample is required for analysis to determine the ratio of fat to marker in the stool and by comparison to the same ratio in the test meal, calculate the fraction of fat absorbed from the test meal. Sucrose behenate is an excellent marker for this purpose because it is currently consumed in food, is completely excreted, is handled by the G.I. tract as are normal dietary fats and is readily measurable by gas chromatography. Thus, this method provides a rapid and easy assessment of dietary fat absorption and avoids the cumbersome and laborious process currently in use. Investigators are currently nearing the completion of a study to compare the method with the quantitative fecal fat measurement in cystic fibrosis and have completed studies evaluating the sucrose behenate method against the quantitative fecal fat method in overweight adults taking Orlistat.

098021 - hBub1, Cell Cycle Checkpoint Gene

Kellen.Sensor@uc.edu (Kellen Sensor) — Thu, 14 Jan 2010 00:00:00 GMT

The present invention provides therapies of human cancers which have a mutation in the hBub1 gene, including gene therapy, protein replacement therapy and protein mimetics. The invention further provides methods for the screening of drugs for cancer therapy . Finally, the invention provides methods of screening of the hBub1 gene for mutations, which are useful for diagnosing the predisposition to cancer. This invention also provides an isolated polynucleotide comprising all, or a portion of the hBub1 locus or of a mutated hBub1 locus.
Genetic analyses have identified six distinct genes (BUB1, 2, and 3 and MAD1, 2, and 3) that are important in regulating the spindle checkpoint. BUB1 encodes a protein serine/threonine kinase and is itself phosphorylated when the cell enters mitosis. A recent study shows that Bub1p activates the spindle checkpoint in the budding yeast. BUB2 is structurally related to the fission yeast cdc16 gene product, which plays an essential part in cytokinesis. BUB3, unrelated to any other known proteins, appears to be a substrate of BUB1.
This technology is patented, and we are seeking a licensee to pursue development of products based on this technology.

109001 - A Safer Way to Treat Obesity

Kellen.Sensor@uc.edu (Kellen Sensor) — Mon, 09 Nov 2009 00:00:00 GMT

Bariatric surgery (also known as weight loss surgery) is performed on obese patients who are unable to reduce weight by dietary modifications or exercise regimens. Current bariatric surgical procedures predominantly involve removing a significant part of the stomach (such as Sleeve Gastrectomy), or partitioning the stomach with incisions and stapling. This may be achieved with or without the re-routing of the food pathway. Some of these techniques are irreversible, a fact which is troublesome in view of the increasingly younger population of potential patients. When reversible, these procedures involve a significant amount of dissection with risks of bleeding and delayed complications. There is also a possibility of gastric erosion, as in the case of gastric banding procedures.

Invention
A surgeon at the University of Cincinnati has designed a device that can overcome many of the shortcomings of current bariatric surgical procedures. The device is flexible and can be used to replace either of the currently used procedures.
The invention has the following advantages over current procedures:

Reversibility

Preservation of gastric integrity

Minimal surgical dissection and reduced operating time

Compatibility with a laparoscopic approach

Further information regarding this invention can be obtained under a Confidential Disclosure Agreement.

106026 - Molecular Profiling of Thyroid Cancer

Kellen.Sensor@uc.edu (Kellen Sensor) — Mon, 02 Nov 2009 00:00:00 GMT

This invention provides methods for characterizing thyroid tissue by detecting the gene expression levels for certain genes, such as kallikrein 10 and claudin 1, among others. This provides a novel approach for detecting thyroid carcinomas by detecting altered gene expressions in thyroid tissue samples (relative to expression levels in normal thyroid tissues). Furthermore, the level of specific gene expression can be used to discriminate between the different types of thyroid cancer e.g., papillary versus follicular.

102080 - The Magnetic Hip Joint For Reduction of Friction

pinskig@ucmail.uc.edu (Geoffrey Pinski) — Wed, 03 Jun 2009 00:00:00 GMT

When pain due to severe osteoarthritis as well as conditions such as inflammatory arthropathies, post traumatic arthritis, vascular necrosis, and childhood diseases of the hip becomes intractable and, recalcitrant to conservative non-surgical management including medication and activity modifications, total hip replacement (THR) is an extremely effective option. It relieves debilitating pain and restores function to hips. Over 120,000 total hip replacements are performed each year in the United States alone. .
However, the longevity of THR is limited by periprosthetic osteolysis. Periprosthetic osteolysis is defined as bone resorption about a prosthetic joint, which occurs as the biological response to particular wear debris from the prosthetic joint. It is the most common and most important long-term complication of THR. The failure of THR necessitates difficult revision THR.
We, at the University of Cincinnati, have developed the technology, which will make Periprosthetic osleolysis a thing of the past. The new approach developed here will prevent/reduce contact at the femoral head /acetabulum and thus significantly reduce generation of particular wear debris and its resultant periprosthetic osteolysis.

Advantages:
1. Commercialization of this technology offers great opportunity to address the needs of a vast population of patients suffering from various joint problems, which are beyond non surgical management; waiting for a solution like this one, which offers effective, long-term cure to the pain.
2. The use of magnetic levitation significantly decreases the generation of particular wear debris. Thus by elimination of particular wear debris from the femoral head/acetabulum in THR and the potential to significantly extend the clinical lifespan of THR.
3. Use of magnetic levitation eliminates/reduces the need for a revision THR. The revised THR is not just more complex, difficult and problematic than the primary THR due in great part to the loss of bone stock caused by osteolysis; its results are generally less satisfactory than primary THR.

108104 - Drug/Food Self-Administration v.2.23

pinskig@ucmail.uc.edu (Geoffrey Pinski) — Tue, 23 Dec 2008 00:00:00 GMT

This software and accompanying bioassay measure the pharmacodynamic (“PD”) and pharmacokinetics (“PK”) properties of a psychotropic compounds. Three properties of the compound can be measured: bioavailability, potency, and half-life. The compound’s potential for abuse/addiction can also be quantified.

Conventional analytical methods for measuring PD and PK properties are time-consuming and cumbersome. In order to measure these properties by conventional means, blood must be sampled numerous times and then later analyzed by chemists using expensive machines and complex techniques. Using conventional methods screening large numbers of compounds is expensive—approximately $100k-$500k per compound.

Conversely the bioassay and accompanying software drug compounds can be quickly, more precisely and cost-effectively analyzed. Using this system, researchers can identify compounds with the longest half-life, the greatest bioavailabilty, those that cross the blood-brain barrier, and those that are the least likely to be habit-forming. The cost of testing a single compound using this bioassay is estimated at $10k-$50k per compound.

This system relies on the pharmacological theory that competitive antagonists increase the concentration of agonist required to produce a response. The response used in this method is the satiety threshold. Increases in the satiety threshold reflect the PD potency of the antagonist in vivo. The time course of the effect reflects the antagonist PK. And the area under the time-concentration curve (AUC) following different routes of administration (e.g., i.v., subcutaneous, or intraperitoneal) measures the bioavailability of antagonists.

For the bioassay, rats are trained to self-administer indirect or direct agonists such as cocaine apomorphine. Once a baseline satiety threshold is established the rats are given doses of the compound to be evaluated. Changes in the frequency of the rats’ self-administration and satiety threshold are measured and from the changes the PK and PD of the compound are be calculated.

The sensitivity of this system is approximately 50-100 fold greater than conventional methods. Conventional methods have a typical limit of detection (LOD) of GC/MS is 1,540 nmol/kg i.v. dose, assuming a volume of distribution of 10 L/kg. This system works optimally at 20 nmol/kg i.v. dose.

Software Requirements:
MS Windows XP
MS Access
MED-PC (Software for testing and collecting data from medical devices)
MPC2XL (For transferring the contents of MED-PC® data files to Excel spreadsheets, Access databases, etc.
Sigma plot (Graphing software)

107054 - Novel End-Point Assay for Autophagy

geoffrey.pinski@uc.edu (Ellen Monson) — Fri, 29 Aug 2008 00:00:00 GMT

Dr. Patrick Dennis at the University of Cincinnati developed a novel end-point assay for autophagy based on the observation that the BHMT (betaine homocysteine methyl transferase) enzyme is degraded via autophagy with the generation of a discrete proteolytic fragment in the lysosomal compartment (1). Dr. Dennis engineered a novel Glutathione-S-Transferase (GST)-BHMT reporter with targeted mutations that result in degradation of the fusion protein via the autophagocytic pathway. Autophagocytic degradation of the reporter leads to the generation of discrete proteolytic fragments in the lysosomal compartment, similar to native BHMT. The advantages of this autophagy assay over existing assays are 1) end-point assay rather than mid-point assay, 2) increased sensitivity and 3) less subjective and more quantifiable.

106078 - Polo-like kinase 3 (Plk3) as a Rational Target for Anti-Cancer Therapy

geoffrey.pinski@uc.edu (Ellen Monson) — Fri, 29 Aug 2008 00:00:00 GMT

A strategy for developing anti-cancer therapies is to inactivate proteins that are required for the integrity of DNA repair signaling pathways. Inactivation of such proteins may lead to greater therapeutic effectiveness of the many current cancer treatments that act by causing DNA damage, such as radiation therapy and many chemotherapeutic agents. When cells incur damage in the form of DNA double strand breaks, normal cells will arrest at various checkpoints throughout the cycle to allow for DNA repair. Several pathways are involved in a DNA damage checkpoint at the G1/S phase cell cycle boundary. One pathway is mediated by the p53 tumor suppressor. P53 induces the kinase inhibitor p21, resulting in the arrest of cells at G1/S. This pathway is compromised due to mutation or loss of p53 in about 80% of human tumors.
The regulation of a second pathway has recently been discovered in the laboratory of Dr. Peter Stambrook at the University of Cincinnati. For cells to activate the G1/S checkpoint, CDC25A phosphatase must be degraded. Using cultured mammalian cells and mouse knockout models, Dr. Stambrook’s work has demonstrated that Polo-like kinase 3 (Plk3), a member of a conserved family of serine/threonine protein kinases, is likely the principle kinase required to facilitate the degradation of CDC25A at the G1/S checkpoint.
Therefore, Plk3 is proposed as a novel target for the discovery of inhibitory molecules that would be useful as cancer therapeutics. The rationale is that most human tumors are p53 deficient and therefore one of the pathways leading to G1 checkpoint arrest is compromised. If the alternate pathway is also compromised by inhibition of Plk3 by a small molecule inhibitor, the tumors would be selectively killed or sensitized to low levels of standard chemotherapies.

104062 - Glucocorticoid Induced Receptor: A novel Neuropeptide Y “Y2-like” GPCR as a target for obesity

geoffrey.pinski@uc.edu (Ellen Monson) — Fri, 29 Aug 2008 00:00:00 GMT

The glucocorticoid-induced receptor (GIR) is an orphan G protein-coupled receptor. GIR was originally identified as a stress-responsive element from the murine T-cell line WEHI-7TG and normal thymocytes treated with glucocorticoids and forskolin. The mouse and rat GIR genes show high levels of expression in the brain. GIR mRNA distribution in the rat indicates a potential role of this receptor in the control of feeding and ingestive behavior, regulation of stress and emotional behavior, learning and memory. The human GIR gene (87% identical to rodent) also shows high levels of expression in the brain.
Rat GIR exhibits highest sequence similarity to the Neuropeptide Y (NPY)-Y2 receptor (38% identity). In experiments to characterize the pharmacology of rGIR, Dr. Randy Sallee and colleagues at the University of Cincinnati, showed that NPY-Y2 selective antagonists and agonists bind to and activate rGIR in a manner similar to NPY-Y2. However, the binding profiles of NPY and Y2 selective ligands to rGIR are distinct from NPY-Y2 receptor suggesting that GIR may represent a novel neuropeptide receptor that interacts with NPY analogs. Indeed, a novel amino acid peptide, the structure of which was modeled on the Neuropeptide Y (NPY) C-terminus, binds with nM affinity to the rGIR receptor but does not bind to any known NPY receptors.Administration of this novel peptide i.c.v. to rats results in feeding inhibition.
Based on a) its distribution in feeding regulatory areas in the forebrain and brain stem, b) its interaction with compounds such as PYY3-36 and other anorectic peptides that regulate feeding, and c) its regulation by leptin, it is likely that GIR represents a novel target for the identification of potential obesity therapeutics.Dr. Sallee’s group has identified small molecule antagonists and agonists of GIR that are currently being tested in animals. These molecules can serve as the basis for the further development of novel GIR antagonists as potential appetite suppressants for the treatment of obesity.