Research

Research Grant Program

NORD’s Research Grant Program provides seed money in small grants to academic scientists studying new treatments or diagnostics for rare diseases. The clinical researchers supported by NORD’s research grants provide preliminary data indicating that a treatment (drug, device, or medical food) may be safe and effective when used for a larger number of patients. Researchers can then use the preliminary data to apply for larger multi-year government grants or to attract a commercial sponsor who will manufacture an orphan product and get it approved for marketing by the U.S. Food & Drug Administration (FDA).

Rare disease research funding opportunities being made available through NORD.

Rare disease research funding opportunities being made available through NORD Member-Organizations.

Read NORD's Research Program Policy to learn how NORD helps individuals, families, groups, or organizations sponsor research.

October 2004 Research Awards

NORD wishes to congratulate and acknowledge the individuals, families, organizations and companies who, through their generosity and commitment, have made these twenty research projects possible.

NORD research awards for Adenoid Cystic Carcinoma:

Mark Darling, MD
University of Western Ontario, London, Ontario, Canada
"Polymorphous low-grade adenocarcinoma (PLGA),
Adenoid cystic carcinoma (ACC) and Pleomorphic Adenoma:
An objective and statisical immunohistochemical comparative study"
Dr. Mark Darling of the Department of Pathology, University of Western Ontario, will study a large number of human kallikreins in normal salivary gland tissue and salivary gland cancers, with particular reference to adenoid cystic carcinoma. This study will show if any of these kallikreins can be used as biomarkers for salivary gland tumors. Dr. Darling hopes to show that the kallikreins could predict outcome and help with future treatment directions of these tumors.

Barry Ziober, PhD
University of Pennsylvania, Philadelphia, PA
"Genomic Analysis of Adenoid Cystic Carcinoma"
Dr. Barry L. Ziober at the University of Pennsylvania, Department of Otorhinolaryngology, will study the genetic changes that occur in patients with the rare salivary gland cancer adenoid cystic carcinoma (ACC). It is well established that cancer is caused by changes that occur in the genetic material present in all human cells. Because of its rarity, little is known about the genetic changes that contribute to ACC. Dr. Ziober's goal is to identify these changes associated with ACC. It is hoped that this work may lead to new ways to identify patients who might develop ACC and provide information toward the development of treatments for patients with ACC.

NORD research award for Cockayne Syndrome:

Edward Neilan, MD, PhD
Children's Hospital Boston, Boston, MA
"Clinical DNA Diagnostic Testing for Cockayne Syndrome
And Functional Analysis of Pathogenic Mutations"
Co-Investigator:
Bai-Lin Wu, Ph.D.
Dr. Edward Neilan and his colleagues at Children's Hospital Boston will develop the first clinical DNA diagnostic tests for mutations causing Cockayne syndrome. They will then seek to determine whether correlations exist between specific types of mutations and the clinical and/or biochemical manifestations of this disease in individual patients. This study should help to determine which parts of the CSA and CSB proteins have essential functions, and it should also help to clarify the clinical spectrum of Cockayne syndrome. Key collaborators in this project include Dr. Bai-Lin Wu at Children's Hospital Boston and Dr. W. Clark Lambert at UMDNJ-New Jersey Medical School.

NORD research award for Creutzfeldt Jakob Disease:

Larisa Cervenakova, MD, PhD
American Red Cross, Jerome H. Holland Laboratory, Rockville, MD
"Differential proteome-based approach for development of assay for early detection of transmissible spongiform encephalopathies using transgenic mice: Model for identification of vCJD-infected individuals".
Drs. Larisa Cervenakova and Serguei Soukharev of the American Red Cross Research and Development Laboratory will use a novel proteomic approach, developed and tested at the laboratory, to study variant Creutzfeldt-Jakob disease (vCJD), the human correlate of bovine spongiform encephalopathy (BSE, sometimes referred to as "mad cow disease"). Proteomics is a relatively new field of study that analyzes the total protein content of infected cells in order to detect differences from healthy cells. By applying proteomic technologies to blood from a mouse model for vCJD infection, the scientists hope to identify proteins related to vCJD that may function as early markers of infection. This research may expand our understanding of transmissible spongiform encephalopathies (TSEs), a group of devastating brain diseases that includes vCJD and BSE. These diseases are understood to be caused by prions, specialized proteins in the brain that may induce disease by changing their molecular shape. The goal of the studies is the eventual development of a test for early diagnosis of TSEs.

NORD/Ehlers Danlos National Foundation research awards for Ehlers-Danlos Syndrome:

Peter Byers, MD
University of Washington, Seattle, WA
"Structural studies of arteries by quantitative MRI in vascular Ehlers-Danlos Syndrome (EDS type lV): genotype/phenotype characterization"
Dr. Peter Byers and his colleagues (William Kerwin, Ulrike Schwarze and Melanie Pepin) of the University of Washington School of Medicine (Seattle) will use high-resolution MRI to study major arteries in individuals with the vascular form of Ehlers-Danlos syndrome (EDS) in an effort to determine if certain types of drugs would be most likely to reduce the risk of arterial rupture, the usual cause of premature death in affected individuals. The vascular form of EDS, EDS type IV, is a rare disorder that affects about 1/100,000 individuals and results from mutations in the type III collagen gene, COL3A1. Affected individuals die prematurely from arterial rupture. Currently there are no effective therapies. These investigators hope that study of the vascular wall by non-invasive techniques (MRI) will help to define new and effective treatments.

Richard Wenstrup, MD
Cincinnati Children's Hospital Research Foundation, Cincinnati, OH
"High throughput analysis of extracellular matrix gene expression in connective tissue disorders"
Dr. Richard Wenstrup, of Cincinnati Children's Hospital Medical Center, will investigate the genetic causes of the various types of Ehlers-Danlos syndrome (EDS). EDS is characterized by looseness of the joints, which can result in painful joint dislocations and early-onset arthritis. The various types of EDS can be differentiated, based on the degree of joint looseness, skin changes and other specific findings. Using the newest techniques, Dr. Wenstrup will screen many expressed genes for a reduction in gene activity, a common cause of EDS, in order to identify new causative genes for the disorder.

NORD research awards for Giant Hypertrophic Gastritis:

John Kao, MD
University of Michigan Medical School, Ann Arbor, MI
"The mechanism of Helicobacter pylori induced
Giant Hypertropic gastrology"
Dr. John Kao of the University of Michigan Medical School will examine the role of Helicobacter pylori in giant hypertrophic gastropathy. Giant hypertrophic gastropathy is a variety of proliferative, inflammatory, and infiltrative conditions associated with large or giant mucosal folds in the stomach. Dr. Kao will study H. pylori infecetion as a potential cause of giant hypertrophic gastritis and establish a mouse model to understand the pathogenesis of this rare disease.

Andrea Todisco, MD
University of Michigan, Ann Arbor, MI
"Mechanisms of Growth Factor Actions in the Stomach"
Dr. Andrea Todisco of the University of Michigan will investigate the molecular mechanisms that lead to the onset of giant hypertrophic gastritis. This rare and debilitating disease is characterized by loss of the cells that produce gastric acid and by the development of giant, hypertrophic gastric mucosal folds. Dr. Todisco's studies will attempt to shed new insights into the mechanisms that lead to the development of this poorly characterized condition. It is hoped that the results of his investigations will represent the first steps for the development of new diagnostic and treatment strategies for giant hypertrophic gastritis.

NORD research award for Kearns-Sayre Syndrome:

Jeffrey Towbin, MD
Texas Children's Hospital, Houston, TX
"Evaluation and Treatment of Cardiac Disease in Kearns-Sayre Syndrome"
Dr. Jeffrey A. Towbin of Texas Children's Hospital and Baylor College of Medicine will study Kearns-Sayre syndrome, a disease affecting the energy-producing units of the body called mitochondria. This disease involves problems with the heart, eyes, muscles, hearing and neurologic systems. Dr. Towbin, a pediatric cardiologist, plans to use new methods to diagnose the heart problems early in these patients and develop new early treatment approaches to improve survival.

NORD/NBIA Disorders Association research award for
Neurodegeneration with Brain Iron Accumulation (NBIA):

Susan Hayflick, MD
Oregon Health & Science University, Portland, OR
"New Gene Discovery in NBIA"
Dr. Susan Hayflick of Oregon Health & Science University plans to identify a new gene causing neurodegeneration with brain iron accumulation (NBIA). Dr. Hayflick and her collaborators found the first gene causing NBIA in 2001, called PANK2, which accounts for about half of the cases of NBIA. With the help of DNA samples from NBIA families around the world, Dr. Hayflick and her team will first find the location of a second gene within the set of human chromosomes. After honing in on a location, the researchers will use new technologies to find the gene, characterize its genetic sequence and start to learn about the job it performs.

NORD research awards for Olivopontocerebellar Atrophy (OPCA) and
Closely Related Neurological Disorders:

Alfredo Brusco, PhD
University of Turin, Torino, Italy
"Identification of the gene responsible for a novel form
of autosomal dominant spinocerebellar ataxia"
Dr. Alfredo Brusco of the University of Turin (Italy) will study the genetics of a novel form of hereditary ataxia, characterized by lack of motor and ocular coordination. Dr. Brusco's goal is to map the genomic region containing the defective gene, and ultimately to identify it. This work may improve the differential diagnosis of hereditary ataxias and shed new light on the pathogenic mechanisms of these diseases.

Gwenn Garden, MD, PhD
University of Washington, Seattle, WA
"Treating Ataxia in a Murine Model of SCA-7"
Dr. Gwenn Garden of the Neurology Department at the University of Washington will institute several pre-clinical trials of potential treatment modalities for an inherited form of cerebellar degeneration called spinocerebellar ataxia type 7 (SCA7). Using genetic engineering, investigators at the University of Washington have generated a mouse model of this disease that demonstrates many similarities with the human disease, including progressive vision loss, unsteady gait and degeneration of specific neurons within the mouse nervous system. Dr. Garden's group will continue study of several changes they have observed in SCA7 mice including loss of important growth and survival promoting proteins from the regions where degeneration develops, imbalances in chemicals called neurotransmitters that govern communication between neurons and activation of the immune system in affected brain regions. They plan to instigate treatment trials in mice that are aimed at preventing or reversing these changes to determine whether correcting the observed alterations can prevent the neurological deficits that eventually develop in SCA7 mice.

Harry Orr, MD, PhD
University of Minnesota, Minneapolis, MN
"Pharmacologic modulation of ataxin-1 phosphorylation"
Dr. Harry Orr and Dr. Michael Kaytor of the University of Minnesota will investigate the mechanism of pathogenesis in the rare inherited neurodegenerative disorder spinocerebellar ataxia type 1 (SCA1). This group previously identified a phosphorylation site on the mutant protein that plays an integral role in disease. They have developed a biological screen to identify small molecules that modulate this protein alteration. The results of this screen will further understanding of the disease SCA1 and has the potential of leading to therapeutics.

Blair Leavitt, MD
University of British Columbia, Vancouver, British Columbia, Canada
"Identifying New Genes Causing Spinocerebellar Ataxias
with an Integrated Clinical, Molecular Genetic and Bioinformatics Approach"
The overall goal of this proposal is the identification of new genetic mutations causing spinocerebellar ataxias (SCAs) to enable development of diagnostic tests and genetic counseling for patients and their families. Two major problems faced by the community of people affected by rare disorders are a delay in, or lack of, specific genetic diagnosis and difficulty in accessing relevant research information. We propose to specifically address these needs by:
(1) Identifying new SCA-causing genetic mutations using a novel candidate gene approach. DNA from patients clinically diagnosed with SCA, but without a defined genetic diagnosis, will be screened for the presence of a specific mutation (CAG trinucleotide expansion) in a large set of candidate genes we previously identified using a genome-wide computational approach. (2) Developing a publicly accessible website (http://www.bioinformatics.ubc.ca/gems/) to provide our information on the 66 SCA candidate genes in the human genome and their characteristic variation in the healthy population, against which mutations can be distinguished. This project is a clinical research study that will advance the diagnosis and treatment of hereditary forms of ataxia.

Dingbo Lin, PhD
Kansas State University, Manhattan, KS
"Mutations of PKCgamma in spinocerebellar ataxia
cause altered cell gap junctional communication"
Dr. Dingbo Lin of Kansas State University will focus on alteration of cell-to-cell gap junctional communication by mutation of protein kinase C gamma, which is unique to neural tissue such as brain and peripheral nerves. Mutation of PKC gamma causes a form of dominant spinocerebellar ataxia (SCA) in human beings. Dr. Lin will reproduce these mutations to investigate how they make neural cells more sensitive to oxidative stress by improper closure of gap junctions. Dr. Lin will also develop synthetic peptides to activate the SCA mutant PKCs, thereby, causing inhibition of gap junctional communication which in turn enhancing resistance to oxidative stress in mammalian cells.

Mario Mascalchi, MD, PhD
University of Florence, Viale Pieraccini Firenze, Italy
"Functional MR imaging of inherited and sporadic
olivopontocerebellar atrophy. Correlation with clinical
and MR markers of disease severity"
Prof. Mario Mascalchi of the University of Florence in Italy will perform a magnetic resonance study of brain function in patients with inherited or sporadic olivopontocerebellar atrophy (OPCA). OPCA is the most common degenerative disease of the brainstem and cerebellum in adults, and is characterized by progressive unsteadiness of gait and loss of coordination. Prof. Mascalchi's goal is to explore the modifications of brain activation in patients with OPCA performing simple and complex motor tasks and to assess possible correlation of these changes with the severity of the brainstem and cerebellar atrophy and of the neurological deficit. This study should provide new insights into the mechanisms of the disease and may contribute to definition of new therapeutic strategies for OPCA.

Tohru Matsuura, MD
Baylor College of Medicine, Houston, TX
"Characterization of the SCA10 ATTCT expansion"
Dr. Tohru Matsuura of Baylor College of Medicine will study the sequence configurations of spinocerebellar ataxia type 10 (SCA10) mutations, using newly developed techniques. SCA10 is a rare form of dominantly inherited ataxia caused by large expansion of a unique pentanucleotide repeat (ATTCT) on chromosome 22. The data obtained will be useful towards understanding the unique instability pattern characteristic of SCA10 as well as for molecular diagnosis and genetic counseling of patients and their family members.

Puneet Opal, MD, PhD
Northwestern University, Chicago, IL
"Cellular pathogenesis of SCA-1"
Dr. Puneet Opal of Northwestern University Medical School will study the cellular pathogenesis of spinocerebellar ataxia type 1. He will focus his efforts on elucidating the neuronal properties of the leucine-rich acidic nuclear protein, a candidate mediator of toxicity in this hereditary form of ataxia.

Ryuji Sakakibara, MD, PhD
Chiba University, Chiba, Japan
"Sphincter function and quality of life in patients with multiple system atrophy"
Dr. Ryuji Sakakibara of the Neurology Department, Chiba University (Japan), will study sphincter function and quality of life in patients with multiple system atrophy (MSA). MSA is characterized by postural hypotension and profound sphincter dysfunction of possible neurogenic etiology. Dr. Sakakibara's goal is to define the mechanism of sphincter dysfunction and its impact to the quality of life in patients with MSA, and to treat them with novel pharmacological modalities.

NORD research award for Tyrosinemia Type 1:

Robert Tanguay, PhD
Universite Laval, Ste-Foy, Quebec Canada
"Evaluation of glutathione monoethyl ester as
therapy for hereditary tyrosinemia type 1"
Dr. Robert M. Tanguay of l'Université Laval (Québec) will test the effectiveness of glutathion supplementation in the treatment of hereditary tyrosinemia type 1 (HT1) in an animal model of the disease. HT1 is a severe metabolic disorder of the liver characterized by extensive liver damage coupled with renal and neurological problems in the first year and an elevated risk of developing liver cancer. While rare worldwide, HT1 shows a high incidence in Eastern Québec with 1 child affected in 1900 births. Dr Tanguay's goal is to provide the liver with a complementary natural defense to prevent liver cancer.