One of the most powerful substances known to promote the maintenance of synaptic connections is a protein called brain-derived neurotrophic factor, or BDNF. BDNF, like most proteins, would not cross the brain’s protective barrier if it were simply administered as a drug. In its natural protein form, BDNF also would be likely to have side effects. My research team pioneered the development of small molecules that mimic key features of BDNF. These small molecules can get across the brain barrier and prevent degeneration of synapse and other Alzheimer’s related events — without producing the potentially harmful effects of high levels of BDNF. We also know that BDNF decreases with age. By adding back its positive effects, we hope to save those synapses. Studies in mice with Alzheimer’s are going well. Our goal is to complete studies that will allow us to start clinical trials.
Most recently, a research team lead by another Stanford neurologist, Tony Wyss-Coray, PhD, built upon the work of Thomas Rando, MD, PhD, a Stanford expert in the biology of aging, showed that the cognitive abilities of old mice could be improved with an infusion of blood from young mice. Wyss-Coray and his team discovered that the most crucial element of the blood linked to that improvement was a protein in plasma called colony-stimulating factor 2, or CSF2. That’s another very exciting discovery because CSF2 is already FDA-approved for people who have received bone marrow transplants. From many decades of use, we also know that plasma is safe. Inspired by these mouse studies, another Stanford neurologist, Sharon Sha, MD, MS, is running a trial in which blood plasma, obtained from the Stanford Blood Center from young, healthy volunteers, is being administered to Alzheimer’s patients to determine if that plasma can improve cognition.
In another very exciting research area, neurologist Michael Greicius is discovering genes that appear to protect the brain from accumulations of toxic amyloid and tau. He has identified people well into their 90s whose PET scan show they have normal cognitive function despite having large amounts of amyloid in their brains or the high-risk apoE4 gene generally associated with earlier onset of dementia. Greicius hopes to use his study of these genes to create powerful new preventive treatments, especially for those at particular genetic risk for Alzheimer’s.
We are also looking at new ways to combine some of the medications and treatments we already have to slow the disease process. We know from the example of HIV that although the effects of one drug might be small, a combination of drugs can be highly effective. Our center also collaborates with selected pharmaceutical companies to offer access to trials for study medications that we feel have potential to be beneficial for people with MCI or Alzheimer’s.