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GAITHERSBURG, MD, United States

Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2002

DESCRIPTION (provided by applicant): Current methods for the diagnosis and management of neoplastic disease rely heavily on imaging techniques, such as X-ray, CT scanning and MRI, tissue biopsy and histopathological findings. Much effort has been put forth to identify other less costly and less invasive means for the diagnosis and monitoring of cancers. In certain cases specific molecular tumor markers have been identified that show promise as potential diagnostic and prognostic indicators, but unfortunately, most of these markers lack the requisite specificity and sensitivity. The long-term objective of this research program is to develop immunodiagnostic assays for the detection of the tumor marker, human aspartyl (asparaginyl) beta-hydroxylase (HAAH). Recent work has demonstrated the over-expression of HAAH in a wide variety of malignant tumors, including pancreatic carcinoma, glioblastoma multiforme, hepatocellular carcinoma, and cholangiocarcinoma. Additionally, unlike other potential tumor markers, over-expression of HAAH displays high specificity for malignant cells. The dismal prognosis associated with cancer of the pancreas is because very few of these cancers are found prior to their spread to other organs. To date, no molecular markers for pancreatic cancer have been identified, validated and accepted for clinical use for early diagnosis. The Specific Aims of this proposal are to establish HAAH as a soluble marker for pancreatic cancer, to develop highly sensitive and specific immunoassays for the detection of HAAH in bodily fluids, and to correlate the levels of HAAH in the serum and/or pancreatic juice of individuals diagnosed with pancreatic carcinoma to disease diagnosis and patient outcome.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2002

Increased expression of human aspartyl (asparaginyl) beta-hydroxylase (HAAH) has been observed in multiple tumor types. HAAH in tumor cells is localized to the cell surface. Its over-expression is sufficient to induce cellular transformation, increase motility and invasiveness, and establish tumor formation. As such, HAAH represents an important novel target for cancer therapy. Ideal drugs retain high affinity and strong specificity for their target, characteristics that are often associated with antibodies. Unfortunately, in most cases effective antibody therapeutics have yet to be developed due to inherent problems in antibody selection and relatively low overall affinities. Recent advances in antibody engineering have lead to the "directed evolution" of extremely high affinity single-chain antibody fragments (scFv). The primary goal of this work is the development of high affinity scFv that can inhibit or attenuate the tumor cell phenotype. In this Phase I proposal we will investigate the use of anti-HAAH mAbs for the inhibition of the tumor phenotype, evolve high affinity anti-HAAH scFv and test their ability to inhibit tumor cell function. A future Phase II application will explore the use of these high affinity anti-HAAH scFv for the treatment of malignancies in preclinical animal models and ultimately in human clinical trials.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 107.00K | Year: 2001

DESCRIPTION (provided by applicant): Parkinson's disease (PD) affects 1 percent of the population over 60 years of age and is one of the most common motor disorders. A pathologic hallmark of PD is the deposition of intracellular protein inclusions known as Lewy bodies in the neurons of affected individuals. The protein alpha-synuclein is a primary component of Lewy bodies and recent evidence has implicated alpha-synuclein oligomerization as a key step in Lewy body formation and in PD neuropathology. The ultimate goal of this work will be the development of pharmaceuticals that can inhibit alpha-synuclein oligomerization and thus Lewy body formation and neurodegeneration. In this phase I grant we will identify and characterize peptide-based inhibitors of alpha-synuclein oligomerization. We will study the alpha-synuclein/alpha-synuclein and alpha-synuclein-peptide interactions and identify the structure/activity relationships involved in the peptide inhibition of alpha-synuclein oligomerization. Finally, we will verify the plausibility of using a-synuclein oligomerization inhibitors in a cell culture model of Lewy body formation. This work will lay the foundation for a phase H grant in which we will identify small molecule drug candidates that act as a-synuclein oligomerization inhibitors, and begin pre-clinical testing of both the small molecule and peptide-based drug candidates in animal models of Lewy body disease. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2004

DESCRIPTION (provided by applicant): Alzheimer disease (AD) is the most common form of dementia and primarily affects older individuals. Currently approximately 4 million people in the United States (US) are affected with AD, and that number is expected t


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 880.94K | Year: 2006

DESCRIPTION (provided by applicant): Ischemia/hypoxia is a significant contributor to neurodegeneration. A typical case is ischemic stroke. Currently, more than 4 million people in the U.S are living with the consequences of stroke. Stroke has become the third leading cause of death in this country, a major cause of long-term disability, and a significant burden on public health worldwide. The clinical significance of cerebral ischemia is compounded by the lack of effective neuroprotective treatments that directly inhibit ischemic neuronal death. Therefore development of novel neuroprotectants is a top priority for the prevention and treatment of ischemic diseases. In phase I of this work we identified a novel class of neuroprotective compounds, the the alpha(N)- heterocyclic carboxaldehyde thiosemicarbazones (HCTs), including PAN-811. Panacea Pharmaceuticals, Inc. has licensed the used of this compound and maintains intellectual property rights for its use in neuroprotective therapy. PAN-811 fully blocks hypoxic and ischemic neuronal cell death at a dose of 1 uM in vitro, and reduces infarct volume by up to 59% in the middle cerebral artery occlusion (MCAo) rat model of stroke. It manifests dual mechanistic functions including both Ca2+ -chelation and free radical-scavenging. Our goal is the development of PAN-811 as a clinically available neuroprotective drug, thus, this phase II grant proposal is aimed at the completion of the requisite preclinical studies. A further pharmacologic study of PAN-811 focusing on its neuroprotective mechanism in reference to necrotic and/or apoptotic cell death is proposed. We will also extend our studies with the MCAo model to optimize the route of administration, compare bolus delivery with infusion, further study dosing effects, and determine the window of therapeutic opportunity. Outcomes will initially be measured by evaluating total infarct volume but will include behavioral testing after more complete establishment of these parameters. PAN-811 is currently in phase II clinical trials for another indication, cancer, by Vion Pharmaceuticals, Inc. As such, much is already known about the human toxicology and pharmacokinetics of PAN-811. If the administration route changes to gain maximum efficacy, the toxicity and pharmacokinetics of PAN-811 will be re-evaluated prior to clinical trial. At the end of the phase II period, we expect to submit an IND application to the FDA to use PAN-811 for the treatment of transient ischemic stroke and initiate phase Ib clinical trials.

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