Biography
Dr. Weksler's research focuses on the mechanisms underlying the age-associated changes in the immune system and how these changes contribute to the diseases of aging: cancer, neuro-degenerative diseases, and atherosclerosis. Laboratory studies focus on the effect of age on the dysregulation of the immune system as manifest by the reduced diversity of the B lymphocyte repertoire and the appearance of benign and malignant B cell clonal expansions and monoclonal gammopathy. Thymic involution is the pacesetter of immune senescence and directly affects the generation and function of T lymphocytes and thereby limits the generation of a diverse B cell and antibody repertoire. We have detected the appearance of monoclonal B and T cell in both elderly humans and old mice. The appearance of the “benign” clonal expansions appears to are precursors of late-life leukemia and lymphoma. Finally, the expansion of malignant B cells expansions in old mice can be prevented by administration of T cells from young but not old mice. .
Our clinical studies focus on the immunotherapy of patients with Alzheimer’s disease (AD). We have demonstrated that patients with AD have a lower concentration of free antibodies to the neurotoxic amyloid beta (Abeta) peptide in their plasma. This finding led to the hypothesis that the low levels of anti-Abeta antibodies in the blood of patients with AD make them less able to clear the neurotoxic Abeta from the brain and lead to increased neuron death. The infusion of human immunoglobulins (IVIg) from healthy individuals into patients with AD leads to an increase in the plasma level of anti-Abeta antibodies and a decrease in the level of Abeta peptide in the CSF. Phase I and II clinical studies have suggested that cognitive function and cerebral glucose uptake are maintained in AD patients who receive IVIg compared to placebo over a period ranging up to 24 months. A phase III multicenter study of IVIg therapy of AD is now in progress.
