SEARCH FOR VIRAL CAUSES OF APLASTIC ANEMIA USING VIRAL MICROCHIPS
Dr. Maciejewski has created a very productive clinical research program in bone marrow failure disorders, a group of related diseases that can affect children and adults. These disorders are characterized by various forms of disruption of blood production in bone marrow. Some of the bone marrow failure syndromes may lead to leukemia. This nationally recognized program includes both laboratory research and a clinical component providing patients with the best clinical protocols, most advanced diagnostics, and scientifically-based but compassionate advice.
The Bone Marrow Failure Program specializes in aplastic anemia, paroxysmal nocturnal hemoglobinuria, and myelodysplastic syndrome. Investigations conducted by this program are directly patient-related and aimed at gaining a better understanding of the causes of these diseases in order to generate diagnostic tools, develop effective treatments, and ultimately, to achieve the cure.
PROJECT
In this specific project, we will endeavor to investigate the viral causes of aplastic anemia. Aplastic anemia is a serious disease in which stem cells in the bone marrow are destroyed and fail to produce blood cells. Without blood cells, patients become very susceptible to infections, their blood does not clot, and they have very few red cells to carry oxygen, which results in severe fatigue. Without treatment, aplastic anemia is lethal; even with treatment, however, only a proportion of patients can recover. For many decades, researchers and physicians have attempted to investigate the causes of this disease that strikes, seemingly randomly and without warning, previously healthy children and adults. There is a great deal of evidence that at least a proportion of cases of aplastic anemia can be triggered by a virus that is as of yet unknown. To date, it has not been possible to identify a pathogen responsible for this disease.
GOAL OF PROJECT
In this project, bone marrow failure researchers propose to apply viral chip technology to identify virus responsible for aplastic anemia and ultimately develop diagnostic, therapeutic and preventive measures. Modern technologies have been developed that use little pieces of DNA on a hard surface (known to scientists as a chip, like a microchip in a computer) to study many various aspects of disease, including how our genes are arranged, whether they are turned off or on, and whether a sample of blood or other tissues has been infected by a virus.
The viral chip uses small pieces of DNA that are shared by distinct groups of viruses, and can be used to identify previously unknown viruses depending on what shared genes they contain. The SARS virus was identified using this technology in 2003. Additionally, the XMRV virus, thought to play a role in prostate cancer, was also found using viral chip technology.
With an appropriate investment, this technology may not only enable research in aplastic anemia, the primary goal of this endeavor, but in many other areas as well, including certain types of childhood and adult leukemia, various hematologic diseases, in addition to many other diseases that seemingly strike without reason but may be triggered by yet unknown viruses. Such diseases may include lupus, rheumatoid arthritis, psoriasis and many others. Consequently, establishing of the technology of viral chips would allow research not only of aplastic anemia, but in many other diseases, and may lead to the development of viral chips as routine diagnostic tools.
COST OF PROJECT
The investment needed for this research project is estimated at approximately $140,000. This projected cost includes synthesis of over 11,000 DNA fragments (oligomers) and printing/spotting of the arrays. The applicable platform may include Affymetrix, Illumina or Agilent technology. Synthesis of the fragments or oligomers requires a one-time expense of approximately $90,000. The subsequent printing of the arrays, for which the costs are currently being negotiated, is estimated to be an additional $40-50,000, depending on the technical platform selected. Further, full application of the viral chip technology will require the recruitment a scientist and technologist. The equipment required is already available, but the research may require additional instrumentation. We plan to make this technology available to other researchers at cost, as the initial investment will allow for the generation of a very large number of arrays, decreasing significantly the cost for each subsequent array.
PROJECT STAGES
The stages of the project include:
Establishing of gene chip technology to produce viral chip
Investigation of patients tissue to identify novel virus that is responsible for aplastic anemia
Screening of large number of patients
Development of diagnostic test
Propagation of viral chips technology to be applied to study many of diseases among interested researchers
DNA chip technology, whether in the application of viral or gene chip, will have great impact on research in various diseases, and will ultimately develop as a routine diagnostic tool. Establishing this technological basis will allow for the medical application of gene and viral chips, impact many areas of medicine, and elevate researchers at the Cleveland Clinic to the very forefront of this field.
Make It Happen for Bone Marrow Disease is an independent fundraiser benefiting