"You got us where you want us: All Together in the Alzheimer's Research Center"

Intranasal Insulin Improves Memory
                Decreased insulin signaling in the brain contributes to both memory loss and brain degeneration in individuals with Alzheimer’s disease. However, it is difficult to treat patients with insulin without causing side effects. At the Alzheimer’s Research Center, we developed an intranasal insulin delivery method that targets insulin to the brain without causing unwanted side effects. When sprayed high into the nasal cavity, insulin travels rapidly into the brain along the nerves involved in smell. Our intranasal insulin treatment has been shown by researchers in Germany to improve both memory and mood in normal adults.

                Along with our collaborators at the University of Washington we showed that intranasal insulin improves memory, attention and functioning in patients in the early stages of Alzheimer’s disease and in patients with mild cognitive impairment. Research is now in progress to determine how long the benefit of intranasal insulin can be maintained with prolonged treatment. Our current intranasal insulin clinical trial assess the safety and benefits of this treatment over a six month period using the most advanced nasal spray device for delivering insulin to the brain.
Intranasal Deferoxamine Binds Iron That Accumulates Abnormally In The Brain In Alzheimer’s, Parkinson’s And Other Brain Disorders
                Free iron accumulates abnormally in the brains of individuals with Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury and other brain disorders where the free iron causes oxidative stress and brain damage. Treatment with deferoxamine, an approved generic drug that binds iron, has been found in animals to treat a variety of brain disorders of this type as described below. This is an example of repurposing an existing drug to treat Alzheimer's disease, Parkinson’s disease, stroke and other brain disorders by using noninvasive intranasal delivery to bypass the blood-brain barrier and target the drug to the brain.

                Along with our collaborators at the San Francisco VA Medical Center, we have discovered that intranasal deferoxamine bypasses the blood-brain barrier to treat and prevent brain damage in animal models of Parkinson's, Alzheimer's, stroke and certain other major neurological disorders. In addition to treating and reducing brain damage from stroke, intranasal deferoxamine significantly improves memory in normal mice and reduces memory loss in mouse models of Alzheimer's disease. It also protects the brain against degeneration and improves movement function in animal models of Parkinson's disease. We are now seeking to test this non-invasive, inexpensive and practical method of treatment and prevention in patients with Alzheimer's disease, Parkinson’s disease, stroke, concussion, hemorrhage, traumatic brain injury and other brain disorders.

               The National Institute of Aging has funded some of the safety studies necessary to enter human clinical trials with intranasal deferoxamine, and the results to date are promising. While a two year clinical trial of intramuscular deferoxamine was shown to reduce cognitive decline in Alzheimer's patients by 50%, there were some side effects. One intranasal deferoxamine safety clinical trial was conducted in humans, and it showed no significant side effects. Intranasal deferoxamine may also be extremely useful to protect military personnel from brain damage associated with closed head injury and for rapid treatment in the field to treat those who have experienced a closed head injury. Similarly, it may be useful to treat auto accident victims who have had a head injury.
Developing Treatments For Alzheimer’s, Parkinson's, Stroke, Multiple Sclerosis, Brain Tumors And Other Disorders Using Intranasal Adult Therapeutic Cells
                Together with collaborators in Germany, especially Lusine Danielyan M.D., Dr. William H. Frey II of the Alzheimer’s Research Center discovered that therapeutic cells, including adult stem cells, immune cells and genetically-engineered cells, can be delivered to the brain using the intranasal delivery method. This method was shown to successfully treat Parkinson's disease in an animal model with intranasal adult bone marrow derived mesenchymal stem cells. Intranasal stem cells bypass the blood-brain barrier to target the brain by traveling along the olfactory neural pathway. Once in the brain, adult stem cells were shown to target the damaged areas of the brain specifically to treat the underlying disease.

               Researchers at University Medical Center Utrecht in the Netherlands have demonstrated the effectiveness of intranasal stem cell treatment in an animal models of neonatal cerebral ischemia, neonatal brain damage and subarachnoid hemorrhage. Researchers at Emory University in Atlanta have used our intranasal stem cell treatment successfully in an animal model of stroke, and researchers at Uppsala University in Sweden have demonstrated that intranasal immune cell therapy reduced symptoms and inflammation in multiple sclerosis. Intranasal adult neural stem cells have also been shown to improve an animal model of multiple sclerosis as have intranasal mesenchymal stromal cells. Still other researchers have reported that intranasal stem cells target and treat brain tumors.

               Along with collaborators, Dr. Frey has also reported that intranasal adult stem cells and other therapeutic cells target the areas of the brain damaged by Alzheimer’s disease in mice. This delivery and treatment method can facilitate the development of adult stem cell, immune cell and genetically-engineered cell therapies for Alzheimer’s, Parkinson’s, stroke, multiple sclerosis, ALS, PSP, Huntington's, neonatal ischemia, brain tumors, traumatic brain injury and spinal cord injury.

               In humans, our own nerve cells are known to reach the brain by using this same olfactory neural pathway during development. In addition, pathologic cells, such as the amoeba Naegleria fowleri found in polluted water, are known to enter the brains of humans by this same pathway and cause amoebic infection of the brain. Fortunately, we have now discovered how to use this pathway to deliver therapeutic cells to the brain to treat brain disorders.