Our objective is to treat patients with osteopetrosis using interferon gamma, (recombinant interferon gamma, Genentech Inc., rIFN) as an alternative to bone marrow transplantation. Patients with osteopetrosis have a defect in bone resorption and leukocyte superoxide generation. In vitro, rIFN stimulates superoxide generation by white cells cultured from patients with osteopetrosis. Our hypothesis is that rIFN may stimulate superoxide generation in cells derived from the G/M progenitor (neutrophils, monocytes, and osteoclasts) resulting in reversal of the defect in bone resorption. Malignant osteopetrosis is a fatal disorder. Without treatment there is a progressive loss of cranial nerve function, marrow space, and abilitity to fight off infection. The risks of this study are based upon the chance of survival and improvement of the disease and the limited additional options. Untreated, deterioration is almost inevitable. There has been a trend toward an increase in bone turnover and cranial foramina size. Decrease in the number of blood transfusions, and increase in mean hemoglobin and platelet count. Without therapy at least 70% die before the age of 2. To achieve our objective we purpose: 1. To evaluate the safety and tolerance of rIFN when administered subcutaneously three times a week to patients with osteopetrosis. 2. To determine whether treatment with rIFN administered subcutaneously three times weekly can improve the clinical status of patients with osteopetrosis with regards to: bone density, (bone turnover, assessed by changes in bone biopsy and biochemical parameters), marrow function and cranial nerve function. 3. To compare these same clinical response measurements in patients treated with either bone marrow transplant or rIFN 4. To determine whether treatment with transplant or rIFN can restore superoxide generation in granulocytes, monocytes, and osteoclasts in patients with osteopetrosis.
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