By Joan Sutton Straus
The best source for information about Alzheimer's, from cause to potential cures, is the NIH website, National Institute on Aging. As I am on the board of overseers of the Alzheimer's Drug Discovery Foundation, (ADDF) I also follow closely its funding decisions. When I raise money for a charity I want to be able to tell those who give, how their money is being used, and how much of it actually gets to the cause. With ADDF, I can tell them that all of their money goes to research because all overhead is paid for by the Lauder family.
Leonard Lauder and his brother Ronald founded the Alzheimer's Drug Discovery Foundation as a public charity in 2004 with one goal -- to develop drugs that would provide more effective treatment for Alzheimer's and lead to prevention and/or a cure. They are determined to accomplish this within the next 10 years.
Since it's founding, ADDF has provided $60 million in funding to 400 programs in 18 countries. One of those projects led to the development of a new brain-imaging test that is now available in the United States and Europe. Using a radioactive drug called Amyvid, this Pet scan estimates beta-amyloid plaque density in adults who are experiencing cognitive loss. A negative scan would suggest that cognitive problems are not the result of AD but some other factor. While a positive scan does not specifically diagnosis AD, combined with clinical information and other diagnostic tools, it can result in a more accurate diagnosis: something that is very badly needed if patients are to be treated effectively.
ADDF's scientific effort today emphasizes the potential in repurposing drugs already on the market. A promising project in clinical trials explores the glucose-insulin needs of the brain. Several years ago, Dr. Suzanne Craft of the University of Washington and Veterans Affairs, Puget Sound, approached ADDF to request funding for an idea that Dr. Howard Fillit, Executive Director and Chief Science Officer of ADDF says "seemed risky at the time." Dr. Craft believed that people with Alzheimer's should be given insulin, delivered through a nasal spray.
Explaining the science behind the initiative, Dr. Fillit points out that although the brain only represents 3 per cent of the body weight, it uses 25 per cent of the oxygen and glucose we consume, for energy purposes. "The brain is extremely metabolically active compared to other organs and very dependent on oxygen and glucose. In order to change glucose into energy, the brain has to have insulin."
He adds, "There has always been a theory that Alzheimer's begins with the aging of a part of the cells that create energy, called mitochondria. With aging, mitochondria become less efficient." He explains "while most organs can replenish themselves -- in the liver, when cells die, new cells are born -- in the brain we lay down circuits early in life and the majority of those circuits don't change, the cells in our brain are as old as we are, they are constantly being ravaged. So the theory that we need new drugs targeted at the mitochondria has been around for a long time.
"Dr. Craft's idea is that -- because insulin enables cell to use glucose more efficiently -- we should be giving AD patients insulin to the brain. But you can't give non-diabetic people insulin systemically because they would become hypoglycemic. She thought that if we could deliver insulin through the nose it would go directly to the brain the same way that cocaine goes directly to the brain, without harmful changes to blood insulin or glucose levels throughout the body. We funded her about eight years ago to create an intranasal delivery system to a pilot study group, to see what would happen to their cognitive function."
The participants were diagnosed with mild to moderate AD or mild cognitive impairment (MCI). Their memory, cognition and ability to function were measured before and after the four months trial period. "And," says Dr. Fillit, "Guess what? Their cognitive function improved and that is unusual. If you look at a lot of the clinical trials, sometimes you will get an outcome on biomarkers, but rarely do you get an outcome for cognitive function."
As a result of initial ADDF funding, Dr. Craft's pilot program has received follow-on funding from the National Institutes of Health (NIH) Institute on Aging and the U.S. Department of Veterans Affairs. Last year, it was one of three projects selected by the NIH to receive $7.9 million of the funding made available by President Obama's National Plan to Address Alzheimer's Disease. For the past year, Dr. Craft and her team have been conducting treatment trials at multiple sites across the United States. The hope is that this insulin spray will have both an immediate affect -- the brain lights up right away -- and a long term one, that the insulin contribution will protect cells from dying.
At the Alzheimer's Association International Conference 2013, held in Boston, Dr. Craft reported "long-acting intranasal insulin imparted a significant memory boost to patients with mild cognitive impairment of Alzheimer's disease who carried a high risk allele for the disease." More study is underway with a one-year program called SNIFF. This will include 240 subjects who will receive insulin or a placebo. Tests of cognition and memory and changes in daily functioning will be assessed at various periods during the study.
Another potential drug repurposing is in clinical trials at the Toronto Dementia Research Alliance at the University of Toronto. ADDF, in collaboration with the W. Garfield Weston Foundation recently announced funding to support a clinical trial investigating the potential for hypertension drugs to slow Alzheimer's disease progression. This study is led by Dr. Sandra Black, who holds the Brill Chair in Neurology at the Department of Medicine, University of Toronto and is the Director of Research for the Brain Sciences Program at Sunnybrook Health Services Center in Toronto.
Announcing the grant, Dr. Fillit explained, "Hypertension has been suggested to be a risk factor for Alzheimer's disease for almost 30 years, yet we have not adequately translated this knowledge into the clinic for the benefit of patients. Dr. Black's study will begin to address this important issue in a novel study design, investigating the possibility that some anti-hypertensive agents may also be neuroprotective."
Once, Alzheimer's was considered to be such a hopeless diagnosis, that no one wanted to put money or scientific effort into drug discovery. Now, thanks to President Obama's National Plan to Address Alzheimer's Disease, and people like the Lauders, Dr. Fillit, and others in the field, that has changed. Getting a drug to market is a long, costly, and expensive venture but, it is happening, and that is good news for Alzheimer patients and their families.