Research

Research Grant Program

September 2002 Research Award Announcements:

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

NORD Research Awards For Adenoid Cystic Carcinoma Adenoid cystic carcinoma (ACC) is a rarely occurring malignant neoplasm that most frequently develops in the minor and major salivary glands in the head and neck region. Other primary sites may include the upper or lower respiratory tract, breast, cervix, or prostate gland. Although ACC has a history of slow growth, it is aggressively invasive and prone to perineural spread, local recurrences, and distant metastases. At the present time, there is no curative therapy.

Dr. Cynthia Jackson and Dr. Douglas Gnepp of Rhode Island Hospital will focus on the identification of genes that are significant in adenoid cystic carcinoma. Genetic alterations play an important role in the development of cancer. The goal of this project is to identify these genes as potentially new prognostic markers, as well as to study their contribution to the development of adenoid cystic carcinoma.

Dr. Eli L. Chang of the Doheny Eye Institute, Keck School of Medicine of the University of Southern California, will concentrate on the establishment of an animal model for adenoid cystic carcinoma of the lacrimal gland. Once an accurate model has been developed, various therapeutic options can be tested on it, perhaps leading to the development of new and improved treatment modalities.

Drs. Robert Greer, Kenneth Shroyer, and Scott Weed of the University of Colorado Health Sciences Center will investigate the prognostic significance of certain genetic changes in ACC at diagnosis, after surgical management, and at disease recurrence in an attempt to identify high-risk patients for potential therapeutic clinical trials, assess whether overexpression of estrogen and progesterone might be a prognostic and therapeutic value in managing ACC, establish clinical outcome measures to better treat patients, and examine the role of cortactin to determine whether its overexpression might be linked to increased metastatic potential of ACC.

NORD Research Award for Mastocytosis
Mastocytosis is a rare disorder characterized by abnormal accumulations of mast cells in skin, bone marrow, and internal organs such as the liver, spleen and lymph nodes. Cases beginning in adulthood tend to involve the inner organs, in addition to the skin, whereas during childhood the condition is often marked by skin manifestations with minimal or no organ involvement. When there is evidence of bone marrow or internal organ involvement, the disease is referred to as "systemic mastocytosis".

Dr. Barry L. Gruber of State University of New York will study the use of a new drug, one of the class of agents known as tyrosine kinase inhibitors, to block the growth of transformed mast cells. Previous studies have yet to demonstrate any substantial effect of this drug in inhibiting proliferation or inducing cell death of transformed human mast cells. Dr. Gruber will re-examine this critical issue and extend the functional studies to probe, in addition, the effect of this new drug on mast-cell migration, which is an important component in the development of disease.

NORD/HSSA Research Awards for Hallervorden-Spatz Syndrome
Hallervorden-Spatz Syndrome is a rare, genetic, neurological disorder characterized by the accumulation of iron deposits in the brain and progressive degeneration of the nervous system. It typically first appears in childhood. Presenting signs and symptoms may include difficulty walking, loss of balance, and problems related to speech. Those affected suffer a progressive loss of muscle control, sudden involuntary muscle spasms, and uncontrolled tightening of the muscles. Symptoms may also include disorientation, seizures, and deterioration of intellectual ability. Most cases have been linked to a mutation of a gene known as PANK2. At the present time, symptoms may be treated, but there is no cure.

Dr. Han-Xiang Deng of the Northwestern University Feinberg School of Medicine will develop a mouse model of Hallervorden-Spatz syndrome (HSS) with the goal of investigating the pathogenesis of HSS and exploring potential drugs for therapeutic testing.

Dr. Susan Hayflick, a medical geneticist at Oregon Health & Science University, will investigate biochemical changes in people with this disorder, which is also known as pantothenate kinase-associated neurodegeneration (PKAN), with the goal of learning how chemical changes contribute to the disease.

DDr. Penelope Hogarth, a neurologist at Oregon Health & Science University, will evaluate clinical measures of disease in people with PKAN, with the goal of providing tools for the assessment of future treatments.

Research awards of April 2002:

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

Primary Lateral Sclerosis (PLS) is a rare neuromuscular disorder characterized by painless but progressive weakness and stiffness of the muscles of the legs. Such weakness may progress to affect the arms and the bulbar muscles at the base of the brain. Less frequently, the muscles of the face are affected. Major symptoms include spasticity, which may result in slow, stiff movements of the legs; difficulty walking and maintaining balance; and cramping of affected muscles. If the muscles of the face are involved, affected individuals may experience dysarthria and dysphagia. In most cases, the disorder affects adults during midlife. The exact cause of PLS is unknown. PLS belongs to a group of neurologic disorders known as motor neuron diseases. The symptoms of PLS occur when motor neurons in the cerebral cortex that control voluntary movements gradually deteriorate.

Dr. Teepu Siddique of Northwestern University has been awarded a research grant for the study of primary lateral sclerosis (PLS) entitled “Molecular Genetic Study of Primary Lateral Sclerosis”. Dr. Siddique identified the first gene known to cause primary lateral sclerosis (PLS) in children, and with collaboration, developed the first transgenic ALS mouse model in 1994. Additionally, Siddique and collaborators discovered the first gene for ALS1 in 1993, and the gene for juvenile inherited ALS (ALS2) in 2001. More than one gene is involved in the development of PLS, however, and Siddique and his laboratory group currently are investigating families with PLS not linked to the same locus.

Dr. John K. Fink of the University of Michigan has been awarded a research grant for the study of primary lateral sclerosis (PLS) entitled “Molecular Basis of Primary Lateral Sclerosis: Search for Alsin Binding Factors”. Dr. Fink’s project will study the relationship between the proteins responsible for juvenile PLS and hereditary spastic paraplegias (HSP), a very similar and often miss-diagnosed disorder.

Multiple Myeloma (MM) is a rare form of cancer characterized by proliferation and improper function of plasma cells. Major symptoms may include bone pain especially in the back and the ribs; anemia resulting in weakness, fatigue, and pallor; renal abnormalities; hypercalcemia; and/or amyloidosis. In most cases, affected individuals are more susceptible to bacterial infections such as pneumonia and urinary tract infections. If the bones of the spine are involved, they may collapse, resulting in spinal cord compression. The exact cause of multiple myeloma is not known. According to reports in the medical literature, multiple myeloma accounts for approximately one percent of all malignancies in Caucasians and about two percent of all malignancies in individuals of African descent. It usually becomes apparent between the fourth and seventh decades of life, with a median age of 68 years at diagnosis. Multiple myeloma is extremely rare before the age of 40. It is believed that approximately 50,000 Americans currently have the disease.

Dr. Mark Ma of Cedars-Sinai Medical Center has been awarded a research grant for the study of multiple myeloma entitled “A Potential Combination Therapy for Multiple Myeloma With Arsenic Trioxide”. Multiple myeloma is a rare form of cancer, characterized by proliferation and improper function of plasma cells. Building on previous studies, Dr. Ma will seek to find a novel treatment for multiple myeloma with the combination of arsenic trioxide and conventional therapy. His goal is to determine the most effective dose, and schedule these combinations for further evaluation in clinical settings.

Dr. Yong-ming G. Tang of Cedars-Sinai Medical Center, California, USA has been awarded a research grant for the study of multiple myeloma entitled, “Evaluation of MAGE-A3 Expression In Patients With Monoclonal Gammopathies”. MGUS is considered to be the early stage or benign form of multiple myeloma (MM). MAGE is a family of genes that has been found to be tumor-specific antigens. Recent findings of Dr. Ma and collaborators show that one member of the MAGE family, MAGE-A3, mRNA was detected in multiple myeloma cell lines, but not in normal lymphocytes, lymphoma cell lines or stromal cell lines. Dr. Ma will measure MAGE-A3 molecules quantitatively at different stages of multiple myeloma to see if the level of MAGE-A3 molecule can be used as an indicator to predict the risk of the development of MGUS to multiple myeloma. Dr. Ma hopes that MAGE-A3 expression profile can be used as a prognostic indicator of multiple myeloma, leading to treatment decisions for specific patients and providing further clues regarding the pathogenesis of multiple myeloma.

Dr. Masato Yamamoto of the University of Alabama at Birmingham has been awarded a research grant for the study of multiple myeloma entitled “Novel Gene Therapy Approach For Multiple Myeloma Using Infectivity Enhanced Adenovirus Vector Expressing STAT-induced STAT inhibitor-1”.

Dr. Yamamoto will use the intrinsic negative feedback factor of STAT-3 signal transduction (STAT induced STAT inhibitory factor-1, SSI-1) as an effector, and employ infectivity enhanced adenoviral vector with integrin-biding RGD motif in fiber-knob region to achieve requisite level of transduction. Dr. Yamamoto’s success may lead to a novel therapeutic modality for multiple myeloma patients.

Pyruvate Dehydrogenase Deficiency (PDD) is an extremely rare disorder of carbohydrate metabolism. Symptoms occur due to a lack of one of the enzymes of the pyruvate dehydrogenase complex and may include severe lactic acidosis, ataxia, choreoathetosis, failure to thrive, and delayed mental and physical development. Affected infants may also exhibit microcephaly and optic atrophy. The disorder is thought to be inherited as an autosomal recessive trait. More than 100 cases have been reported in the medical literature.

Dr. Mulchand S. Patel of the State University of New York at Buffalo has been awarded a research grant for the study of Pyruvate Dehydrogenase Deficiency (PDD) entitled “A Mouse Model for Pyruvate Dehydrogenase Deficiency”. Dr. Patel will develop a mouse model for PDD using gene manipulation and characterize its effects on brain development. The goal of Dr. Patel’s study is to characterize region-specific morphological changes in developing brain of pyruvate dehydrogenase-deficient mice. This animal model will be useful to evaluate the efficacy of pharmacological and dietary treatments.

Kearns-Sayre Syndrome (KSS) is a rare, neuromuscular disorder characterized by three primary findings: chronic progressive external ophthalmoplegia (CPEO); atypical retinitis pigmentosa, leading to pigmentary degeneration of the retina; and cardiomyopathy. Other findings may include muscle weakness, short stature, hearing loss, and/or ataxia due to problems affecting the cerebellum. KSS belongs (in part) to mitochondrial encephalomyopathies.

Dr. Eric A. Schon of Columbia University College of Physicians and Surgeons has been awarded a research grant for the study of Kearns-Sayre Syndrome entitled “Heteroplasmic Shifting As A Strategy To Treat Kearns-Sayre”. Dr. Schon will study pharmacologic approaches to the treatment of Kearns-Sayre syndrome (KSS), a mitochondrial disorder associated with large-scale deletions of mitochondrial DNA (mtDNA). Mitochondria are the main source of energy in cells. In KSS, energetic failure causes skeletal muscle abnormalities, paralysis of the extraocular muscles, hearing loss, diabetes, mental retardation, and ultimately, heart failure due to conduction block. Dr. Schon’s goal is to reduce the amount of deleted mtDNAs in patient tissues, so that the remaining normal mtDNAs can restore energetic function.

Researchers may receive notification of future funding opportunities by submitting a complete mailing address to nwoodage@rarediseases.org.

For information on initiating a research project click here to read NORD's Research Program Policy