Research Spotlight

New Cancer Vaccine Trial Begins at Medical Center
A Big Surprise: Nerve Cells Can Reset Their Developmental Clocks
New Technique Detects Earliest Alzheimer’s Signs in Healthy People
NYU plays key role in FDA’s ok of Alzheimer’s drug

New Cancer Vaccine Trial Begins at Medical Center
Vaccines ordinarily prevent disease, but one type of experimental vaccine is designed with something else in mind: blocking the recurrence of certain diseases, namely, some forms of cancer.

Robin Green, R.N., administers a trial vaccine to Stefan Melnikoff, a patient with follicular lymphoma.

A new clinical trial of one of these vaccines, involving eight hospitals nationwide, recently began at NYU Medical Center. At least 13 patients have enrolled at NYU to date.

The vaccine is unique in that each customized dose incorporates proteins specifically found on each patient’s tumor cells. These proteins provide a target for the patient’s own immune system. The process is a bit like giving a piece of clothing to a bloodhound—the vaccine stimulates immune cells in the body to seek out and destroy malignant tissue carrying the proteins. The vaccine is designed to eliminate any residual cancer cells following chemotherapy, and thereby prevent the disease from recurring.

The NYU trial involves patients with follicular lymphoma, a type of cancer in which abnormal white blood cells multiply and grow into tumors, enlarging the lymph nodes and other sites in the body. Even with chemotherapy, this type of cancer redevelops in virtually all patients. The Leukemia and Lymphoma Society estimates that about 25,000 people will be diagnosed with follicular lymphoma this year.

“Patients with follicular lymphoma are generally diagnosed in their sixties. However, in recent years we have seen an increased incidence in younger individuals, in their thirties or forties,” explains Giorgio Inghirami, M.D., Associate Professor of Pathology, who is one of the physicians leading the clinical trial. The other lead physicians are Franco Muggia, M.D., Director of Clinical Oncology, and Tatyana Feldman, M.D., Clinical Instructor in Medicine. The vaccine was developed at the National Cancer Institute (NCI). In earlier, smaller trials, it prevented recurrence of the cancer in more than 50 percent of cases, many of which are still in complete remission.

A Big Surprise: Nerve Cells Can Reset
Their Developmental Clocks

The bright green spots in these images are cells that normally appear only in layer one of the brain’s cortex, as shown in the top image. When the gene Foxg1 is eliminated from embryonic mice, the bottom image shows the result: These cells now appear in all of the six layers of the cortex.

The brain’s cerebral cortex, made of intricately folded gray matter, is seemingly convoluted. Yet the process by which it develops is surprisingly orderly. This brain region is made up of six layers of cells that grow at a precise time and in a precise sequence. But until now, what controlled this process has remained a mystery.

NYU researchers report in a recent issue of the journal Science that they have found part of the answer. They observed that a gene, called Foxg1, partly controls this orderly production of cell layers.

“What we found was a complete surprise,” says Gordon J. Fishell, Ph.D., Associate Professor of Cell Biology. Dr. Fishell’s team made their discovery by observing which cortical cell layers are generated in embryonic mice that lack Foxg1. Without the gene, all the cells form layer one instead of moving on to layers two through six. In effect, their developmental clocks are constantly being reset to the beginning. Carina Hanashima, Ph.D., a postdoctoral fellow in Dr. Fishell’s laboratory, conducted the experiments.

Are there other genes that control the developmental clock of cortical cells? Dr. Fishell intends to find out. Such research will help answer fundamental questions about the development of the brain and contribute to the understanding of how genes can be manipulated to generate replacement tissue to treat devastating diseases of the brain and spinal cord.

New Technique Detects Earliest Alzheimer’s Signs in Healthy People
Doctors hope to be able someday to reliably identify changes in brain structure and metabolism associated with early Alzheimer’s disease—before symptoms emerge, so that potential therapies might delay or even prevent the devastating brain disease. Now this goal is one step closer to being realized. Using a new technique to measure brain volume, School of Medicine researchers were able to identify healthy individuals who would later develop memory impairment, a symptom associated with a high risk for future Alzheimer’s disease.

In the small study, led by Henry Rusinek, Ph.D., Associate Professor of Radiology, and published in the journal Radiology, the researchers used MRI scans and a computational formula to measure a region of the brain containing the hippocampus and the entorhinal cortex, key structures associated with learning and memory. They found that, over a period of years, this region shrank considerably more in people who developed memory problems than in those who didn’t have such problems.

“I believe that this technique opens an era of early diagnosis of Alzheimer’s disease,” notes Mony J. de Leon, Ed.D., Professor of Psychiatry, Director of the Center for Brain Health, and an author of the study. “Now, we want to combine this technique with measurements of certain Alzheimer’s-related proteins found in cerebrospinal fluid, to get an even more diagnostically specific assessment.”

NYU plays key role in FDA’s ok of Alzheimer’s drug
When the Food and Drug Administration (FDA) approved the first medication to treat the later stages of Alzheimer’s disease last fall, the School of Medicine had good reason to be proud. Six months earlier, NYU researchers had published a study in the new england journal of medicine showing that the medication, memantine, could slow the progression of Alzheimer’s at a time when mental and physical deterioration normally accelerate rapidly. The approval was based, in part, on the nYU study, led by barry reisberg, M.D., and steven ferris, ph.d., both of the silberstein aging and dementia research and treatment center.