Amyloid Research
Primary amyloidosis (as well as other forms of the disease) is the subject of intense scientific investigation. The Human Immunology & Cancer Program (HICP) maintains extensive laboratory and support facilities staffed by dedicated professional and technical personnel who are engaged in research of this disorder. Also participating are international visiting scientists who are among the world's experts in this field. Medical care, including diagnostic procedures, treatment, and consultative services, are provided in a clinic devoted to people with AL amyloidosis. Thus, the patient is a participant and an integral part of the research efforts.
Critical Questions
HICP researchers have formulated medically-based strategies that are designed to answer questions deemed critical to solving this devastating problem:
- How can the diagnosis of the disease be improved?
- What causes certain types of Bence Jones proteins to form amyloid fibrils?
- Why are particular organs or tissues apparently "targeted" for fibril deposition and what accounts for the differences observed between patients in the organs predominately affected?
- How can fibrils be eliminated once laid down or even prevented from forming or depositing?
- Finally, is this disease dependent upon the injurious nature of the protein itself, or do people with this disorder have some sort of defect that causes these proteins to form amyloid, or is a substance lacking that can help remove this material once deposited?
The fact that amyloidosis is not a single disease, but rather is a group of disorders that result from the pathologic deposition of at least 20 different proteins, necessitates that physicians have knowledge of the exact type of amyloid occurring in their patients, since the various amyloidoses have different prognoses and require individualized treatment.
Determining the Type of Amyloid
Because all forms of amyloid are similar in appearance when viewed through a microscope, they can not be distinguished from one another on this basis; thus, alternative methods have been developed and utilized to identify indirectly the nature of this substance. However, to establish unequivocally the particular kind of amyloid present, it is necessary that this material be selectively removed from tissue and analyzed in the laboratory for determination of its exact chemical composition. This can be a formidable task and, until recently, one that required a relatively large specimen to be collected and used for study.
Fortunately, reserachers have now developed a "micro-technique" that makes it possible to gain such information from minute tissue samples obtained by fine needle biopsy or fat aspiration.
Because patient as well as protein factors can be involved in the generation of amyloidosis, The HICP's research also is directed toward elucidation of antibody-related genes and the development of experimental models of this disease. Further, after proteins that make up the amyloid are isolated from tissue specimens and analyzed in the laboratory, HICP researchers can compare them to other samples to determine if amyloid-forming components differ from those that are not involved in this process. Such information can be used as the basis for generation of drugs and other compounds that will be helpful in treatment.
Additionally, work is underway to determine if tissue specific factors are present in particular organs that "attract" or bind light chains and result in fibril formation. If such a structure is identified, agents could be designed that would prevent the binding of light chain proteins to tissues and thus amyloid production would be prevented.
The Body's Natural Defense
The HICP research team also is studying ways to elicit a natural defense response from the body that would eliminate these abnormal deposits before irreparable organ damage occurs. To accomplish this, they have developed certain reagents called monoclonal antibodies that are attracted specifically to the unique structure of amyloid proteins. When these antibodies are given to animals that have primary (AL) or secondary (AA) amyloid deposits, this material disappears rapidly.
HICP's highest priority is to determine if such reagents would be beneficial to patients with AL amyloidosis. In this regard, the National Cancer Institute, through its " Rapid Access to Intervention Development (RAID) " program has agreed to provide the funds necessary to prepare one of HICP's "anti-amyloid" monoclonal antibodies in a form that can be administered to humans, and also to produce a sufficient amount of this clinical-grade reagent for a Phase I/II trial in patients with this disease.
The use of this form of "passive" immunotherapy to remove amyloid deposits would be a major advance in the treatment of AL, as well as other amyloid associated diseases.
These areas of ongoing study that combine patient care and laboratory research ultimately offer hope to patients with primary (AL) amyloidosis. Because each case is unique and offers important information , continued research and careful study of individual patients will help achieve the goal of curing or preventing this devastating illness.
|
