ICVRX treats underserved patients with CNS disease by providing reformulated CNS products as a specialty pharmacy company. ICVRX’s reformulated off patent-generic products are proprietary products administered via implantable pumps. Therapies administered via a technical, development, regulatory and business perspective, ICVRX’s approach in developing drugs is significantly less capital intensive than traditional drug development models. This offers a unique investment alternative that requires modest funds needed for development, and reflects early-term revenues and a shorter-term payback for investors.

Assistive Technology Partners' mission is to assist persons with cognitive, sensory, and/or physical disabilities to reach their highest potential at home, school, work, and community through the use of appropriate Assistive Technologies (AT).

Since 1995, Assistive Technology Partners has provided one-on-one assessments and training on the use of technology to enhance the lives of individuals with disabilities. Current faculty has the expertise in highly specialized areas to meet the AT needs of each individual, regardless of functional limitation or complexity.

Over 500,000 individuals throughout Colorado and the world have been directly served through Assistive Technology Partners' efforts in creating awareness around the diversity of available technologies and services for persons with disabilities. Emphasis continues to be placed on reaching underrepresented populations, including Native Americans, the elderly and rural populations.

With the goal to improve the quality of life of people with disabilities, the research and engineering faculty designs, develops, and conducts projects to generate new scientific knowledge for the field of assistive technology. Research and engineering projects range from product/device development to therapeutic trial investigations.

From raising individual and community awareness around Assistive Technology (AT), to skill development in specific areas or on specific devices, to graduate coursework for professionals, the faculty at Assistive Technology Partners not only has the depth of cross-discipline expertise, they are specialists in applying and integrating Assistive Technology (AT) in the full spectrum of settings. Training opportunities include presentations on site and at conferences across the country and around the world.

Glioblastoma multiforme (GBM) is an incurable form of brain cancer with an average life expectancy of approximately one year. Despite surgical resection and adjuvant therapy, mortality occurs in close to 100% of the patients, presumably due to inherent drug and radio-resistance. Temozolomide has become a chemotherapy of choice for GBM. It induces DNA damage via methylation of DNA at the O6 and N7 positions of guanine, which results in cell cycle checkpoint arrest and apoptotic death. These damages can be repaired by O6-methylguanine-DNA-methyltransferaze (MGMT) unless methylation of the promoter for the enzyme prevents its transcription1,2.

TMZ resistance can also result from TMZ-promoted autophagy3, a condition where the cell consumes its own organelles. Uncontrolled autophagy can promote cell death. However autophagy can also provide a strategy for GBM cell survival and TMZ resistance4. Autophagy has been shown to control fatty acid oxidation 5 and we have strong evidence that FAO in tumor cells protects cells from DNA damage 5.

Mitochondrial uncoupling protein 2 (UCP2) plays a protective role by reducing mitochondrial membrane potential, thereby preventing free radical induced DNA damage. UCP2 acts to depolarize the mitochondrial membrane promoting a shift to fatty acid oxidation, and likely proton translocation during fatty acid transport thereby preventing free radical damage6. Etomoxir, a clinically approved inhibitor of carnitine palmitoyl transferase, suppresses fatty acid oxidation, inhibits the activity of UCP2, and promotes Fas:FasL-mediated cell death by increasing DNA damage in glioma cells. Here we show that both C6 rat glioma and U263 human glioma cell lines espress UCP2, exhibit low mitochondrial membrane potential, and are resistant to many apoptosis-inducing stimuli. We demonstrate that when treated with etomoxir, the cells have increased mitochondrial membrane potential and increased DNA damage. In addition, when combined with TMZ, these genotoxic activities appear to act synergistically to induce even greater DNA damage, concomitant expression of Fas and FasLigand, and, when combined, a significantly increased percentage of cell death.

The ultimate goal of the research program at the Costa lab is to develop drug therapies aimed at helping to improve the quality of life of persons with Down syndrome (DS).  Here, we will discuss potential pharmacotherapies, including our recent results showing that the AD drug memantine can reverse learning and memory deficits in Ts65Dn mice.  Because of these preclinical findings and the safety profile of memantine, and the possibility that memantine may indeed delay the onset of AD-type pathology in young adults with DS, we were able to assemble a group of physicians and psychologists who all agreed that a small-scale randomized controlled clinical trial was warranted at present.  With funding from an investigator-initiated grant (Forest Research Institute), the authors are currently performing a clinical trial titled: “A Sixteen-Week, Randomized, Double Blind, Placebo-Controlled Evaluation of the Efficacy, Tolerability and Safety of Memantine Hydrochloride on Enhancing the Cognitive Abilities of Young Adults with DS.”  A total of 40 persons with DS of both genders and between the ages of 18 and 32 are being recruited in conjunction with the Mile High Down Syndrome Association, the Denver Adult Down Syndrome Clinic, and the Colorado Springs Down Syndrome Association.  The trial is taking place at The Children’s Hospital.   We will discuss the design and current status of this clinical trial, and then indulge in some speculation on the potential impact of this and future clinical trials in the field of DS.

Twitter is a popular free service that lets people post and read short (less than 140 characters) messages called "tweets".  Throughout this year's conference, attendees are encouraged to participate in online discussions using Twitter and the hashtag #cic09, short for Coleman Institute Conference 2009.  A public display of real-time tweets will be set up so those not using Twitter can see what other attendees are saying.  Conference attendees can use Twitter to offer comments, highlight interesting sessions, take notes, link to online resources, and share ideas with other attendees and those not able to attend.  The use of the #cic09 hashtag is encouraged before, during, and after the conference.

Intellectual Disability (ID) affects some 2%-3% of the population of industrialized nations. Genetic causes of ID include (i) mutations in ~300 genes identified to cause ID as primary or secondary events, (ii) Down syndrome, trisomy of the long arm of chromosome 21 (HSA21q), and (iii) gene deletion and duplication in natural Copy Number Variation (CNVs) whose frequency and identity are only now being ascertained. We are developing the ID Gene Function and Pathway Database (https://gfuncpathdb.ucdenver.edu/iddrc/iddrc/home.php) with the goals of: facilitating understanding of the genes which, when perturbed by mutation or gene dosage variation, cause ID; aiding in the description of pathways critical for ID; and identifying novel components of these pathways. Current contents of the database include: (1) A list of ~300 genes obtained from OMIM and identified with mutations causing ID. This list is searchable by disease name, gene name, and genomic location; data retrieved include disease description, gene functional information, mutation description, ID as primary or secondary effect, and genes located in the adjacent genomic regions. (2) A catalogue of ~500 genes identified by genomic sequence annotation of chromosome 21; similar catalogues of genes in the orthologous chimpanzee chromosome 21 and orthologous regions of mouse chromosomes 16, 17 and 10. These catalogues are searchable by gene name, gene functional class, open reading frame characteristics, conservation and genomic location. (3) A catalogue of SNP variation in RefSeq protein coding genes of human chromosome 21; potential functional consequences of SNPs are described based on location with the mRNA and amino acid features of synonymous-nonsynonymous, conserved-nonconserved and location within a protein functional domain. (4) Protein interaction and pathway discovery tools; all pair wise protein interactions have been obtained from the Human Protein Reference Database (HPRD) which compiles manually reviewed data from the literature. The user can formulate queries such as: Do Protein A and Protein B interact directly? What is the shortest interaction path between Protein A and Protein B? What are all the interaction paths (of defined length) from Protein A to proteins involved in ID. Results are obtained in text and graphical displays.

Development of the database is ongoing. Immediate goals include adding novel ID genes from recent reports in the primary literature, refining protein interaction graphics, and incorporating pathways from KEGG.

There is a growing population of older adults with dementia that are residing in long term care settings. These individuals commonly experience difficulty locating their bedroom as a result of cognitive impairment, limited learning histories, and ineffective cues to help distinguish individual bedrooms. Ineffective wayfinding abilities may expose elders to safety hazards and may create problems for other residents and staff. Study 1 investigated the ability of four elders with severe dementia to recognize various self-referent stimuli (i.e., young adulthood photograph, middle adulthood photograph, current photograph, and printed name). Residents that were able to meaningfully recognize at least one type of stimulus then participated in Study 2, which involved an intervention in which the various stimuli (i.e., best recognized stimulus, poorest recognized stimulus, no stimulus) were posted outside their bedroom doorway during assessment probes and room finding abilities were measured using direct observation techniques. Data are presented as accuracy and latency to room finding. Future research that will improve upon the first two studies will be discussed.

Virtual Reality technology can create compelling augmentations for cardiovascular exercise equipment such as treadmills, stationary bikes, or arm ergometers, which can engage users and increase enjoyment and participation in regular exercise programs. The overall goal of this project is to create more motivational, visually-stimulating virtual exercise environments (VEEs) that will promote greater adherence to exercise among people with disabilities. Currently the prototype VEE consists of a recording system to capture video as well as distance and incline data about real trails, and a playback system which "displays" both video and terrain data in the form of video speed and machine resistance.

The VEE trail capture system requires methods for acquiring both multiple video streams and physical measurements of tilt and distance. We have completed our revision of the system developing a new rig using 3 HD camcorders and a handheld GPS unit. The new system blends 3 1920x1080 views into a 140° horizontal field of view panorama (below) for display on one or more large format screens.

The main challenges for our new system have been extracting the required GPS measurements and aligning and blending high quality panorama sequences from the video streams. In order to adequately approximate tilt we require a GPS unit with a pressure-based altimeter. To incorporate this data in VEE playback we developed software to export and decode it on our postprocessing computer.

Generating high quality wide angle panoramas poses several technical challenges. The first step is to estimate the physical geometry of the camera positions in order to compose the individual frames into a single panoramic image. For regions where two frames overlap image parallax can cause nearby objects to appear twice because their image position differs for each frame (viewpoint). Further because of differences in viewpoint and lighting and even small hardware differences the image appearance (color, brightness, etc) can vary between frames. We continue to work on the problems of blending and color correction for our panoramic sequences.

We are also developing a new large format playback system for the VEE which will exploit the (relatively) low cost and availability of large-format HDTVs as the display device. In virtual reality the larger the display the more immersive the feeling of the environment. We will use the latest Microsoft Media Foundation tools to control our wide angle panoramic videos and display them on a display panorama consisting of 3 large screen HTDVs mounted in front of our cardiovascular exercise equipment.

Most low cost stationary exercise machines do not have external interfaces which allow us to read information about speed or control resistance. A new direction for our VEE is to "instrument the person" rather than the machine. To this end we are investigating wearable digital odometers and exercise heart rate monitors in an effort to estimate activity level, or "speed" for a subject in order to control VEE playback.

The mission of the Colorado Intellectual and Developmental Disabilities Research Center (IDDRC) is to conduct research of the highest quality that advances the diagnosis, prevention, treatment, and cure of neuro-developmental disorders and promotes the amelioration and rehabilitation of affected children and adolescents.

The IDDRC is supported by the Eunice Kennedy-Shriver National Institute of Child Health and Human Development, is based in the Department of Pediatrics of the School of Medicine and includes some 40 independent investigators from various clinical and basic-science departments. IDD-focused research funding totals over $15,000,000 per year. The IDDRC provides an infrastructure designed to facilitate IDD research and to promote translational studies. The research core facilities are: (1) Translational Nexus, an IDD-focused patient registry and biobank (storing sera, DNA and immortalized lymphoblasts); (2) Animal Models (providing animal husbandry, genetic engineering, behavioral assessment, and brain imaging services); (3) Cell Systems & Analysis (providing cell culture and neuro-anatomical/histological assistance); and (4) Molecular Discovery (providing technologies and expertise for the analysis of genome, transcriptome, proteome, molecular interactions and structure). The Center's research programs cover all neuro-developmental disorders to the extent possible and integrate studies on cell/molecular disease mechanisms, translational studies involving disease models, and clinical trials. In other words, research reaches from bench to bedside to curbside.

For further information, contact: Karl H Pfenninger MD, Director, karl.pfenninger@ucdenver.edu or google "Colorado IDDRC".

The IDDRC Translational Neuroscience Nexus (Nexus) functions as a searchable database, patient registry and linked biological sample bank focused on a broad range of intellectual and developmental disabilities (IDD). The goals of the Nexus include the following: to advance research and treatment of IDD; to provide data for future research studies; to identify links between genes, cognition and behavior; to facilitate access to appropriate patient cohorts for clinical trials; and, to promote new and competitive research programs at the University of Colorado Denver. On our poster, we outline who can participate as study subjects and describe how researchers can utilize our subject population and linked biological sample bank for research studies focused on IDD. Furthermore, we outline the consultation services we can provide and how we can best be contacted.

For job seekers with cognitive disabilities, it can be a challenge to learn about opportunities and accommodations in the workplace. This  project  aims to explore design considerations towards the development of an effective computer-based tool to support  career exploration for individuals with cognitive disabilities.  We developed a prototype system focusing on mail room and file clerk jobs commonly found in a professional office setting.  The prototype uses photos and an animated agent to convey information in much the same way as a helpful and effective job coach; enabling users to examine and identify jobs that are both interesting and suited to their abilities.  A two phase usability study incorporating both objective and subjective measures of performance was implemented in order to guide further development of the system.  Thirty four individuals with varying degrees of cognitive disability participated in the study.

Neuropsychological assessment tests have been used to evaluate individuals with developmental disabilities and individuals who may experience age-related cognitive changes. We have developed a set of neuropsychological programs with norms for independent functioning individuals between the ages of 5 and 90 years. This battery of tests can be used by individuals with minimal training to detect changes in cognitive abilities over time and provide a basis for seeking professional assessments. We provide an example of how change occurs over time on a single test (Tower of Hanoi) and compare a closed head injured group with age matched controls.

Parkinson's disease is caused by the loss of dopamine neurons in the ventral midbrain.  People with mutations in the DJ-1 gene that prevent DJ-1 protein dimerization will develop early onset Parkinson's.  We have shown that overexpression of DJ-1 can protect dopamine neurons from oxidative stress by selective upregulation of glutathione (GSH) biosynthesis.  If cells are stressed by mutant α-synuclein accumulation, GSH is not increased; instead, heat shock protein 70 production is turned on.  We have found that sodium phenylbutyrate (PB) can increase DJ-1 expression by 200-400% in dopamine cell cultures.  Using our Y39C mutant α-synuclein transgenic mouse model, we have found that PB treatment for 3 months in aging animals (15-18 months) prevented a decline in motor function by increasing brain and plasma DJ-1 concentrations.  Plasma DJ-1 was increased from 3.1 +/- 0.3 ng/ml to 6.5 +/- 0.6 ng/ml with PB of 1 mg/ml in the drinking water (p<0.01).  Increasing PB to 2 mg/ml did not further increase plasma DJ-1.  We conclude that phenylbutyrate can upregulate DJ-1 activity and prevent progression of motor complications in a transgenic mouse model of Parkinson's disease.  Based on these data, we have started a clinical trial of phenylbutyrate in patients with Parkinson's disease.

Supported by the Coleman Institute for Cognitive Disabilities, the Parkinson Disease Foundation, and a gift from Charles and Joanne Ackerman.  Wenbo Zhou, PhD, is a Coleman Institute Scholar.