Retired San Francisco real estate developer Douglas Rosenberg says he has a new job - helping to find a cure for Alzheimer's disease. Through the Ellen and Douglas Rosenberg Foundation, the venture philanthropist is betting at least $3.5 million that Buck faculty Dale Bredesen, MD has the correct take on how to thwart the memory robbing disease that affects over 5 million Americans. The two have formed a unique partnership aimed at developing treatments based on the results of small molecule screenings that show promise in cell culture and animal models of the disease. Rosenberg's goal is to raise at least $10 million to get the new drug candidates into early clinical trials.
"We can't afford to wait, I can't afford to wait," said Rosenberg. "Big Pharma is not stepping up to the plate and the federal government, through the National Institutes of Health, is not providing money for this type of drug development either."
Rosenberg has seen the worst of Alzheimer's. His father, prominent San Francisco businessman and nationally-renowned philanthropist Claude Rosenberg, Jr. died from the neurodegenerative disease in 2008. His stepfather died from the condition that same year. His stepmother succumbed to complications of Alzheimer's in 2010.
A friend invited Rosenberg to hear Bredesen speak at the Stanford Marin Club in November 2007. Rosenberg said he got excited about Bredesen's research. "It was a fresh approach -- he was taking a look at the root causes of Alzheimer's way upstream from other work I was familiar with," said Rosenberg. "Ironically, I had never been to a Stanford function before, so I assumed it wasn't an accident that we met." The two men became friends.
Bredesen, an academic neurologist turned researcher, focuses on Alzheimer's as a disorder involving an imbalance in signaling between neurons that impacts brain plasticity, rather than the current dogma that Alzheimer's is a disease of toxicity stemming predominantly from damage caused by amyloid plaques that collect in the brain. Bredesen believes those plaques are an effect, not a cause of the disease - his theory explains why experimental drugs aimed at getting rid of the plaques have failed repeatedly in clinical trials; his research also points the way toward what he thinks could be the first effective treatments.
Bredesen believes the amyloid beta peptide, the source of the plaques, has a normal function in the brain-a finding that has been missed by the research community. Bredesen says the peptide causes signaling between neurons to contract or pull back, which supports the ordinary and essential memory loss that allows us to forget unimportant things like the seventh song we heard on the radio on the way to work. He says problems occur when the peptide gets out of balance with the nourishing factors that support signaling between neurons - the type of memory-making activity that allows us to remember where we put our keys. "It's the molecular balance between memory making and memory breaking that's critical," said Bredesen. "We found that when that balance is lost, neuron signaling gets stuck in reverse. What is surprising is that the actual chemicals involved in forgetting beget more of themselves - in other words, forgetting multiplies - and if left unchecked, this can ultimately lead to Alzheimer's disease."
To develop therapeutics utilizing this new insight, Bredesen, with Rosenberg's initial funding, hired a highly experienced pharmaceutical chemist, Varghese John, PhD, and together they established the Alzheimer's Drug Discovery Network, centered at the Buck Institute. They have been screening chemical compounds, and have already identified several promising candidates that restore this critical memory balance in "Mouzheimer's," a mouse model of Alzheimer's disease; the group is now completing pre-clinical studies required to move these into clinical trials.
"We are truly grateful for Douglas's support in this effort, and impressed by his knowledge of Alzheimer's disease therapeutic development," said Bredesen. "The funding gap between basic discovery and drug development is commonly called 'the valley of death,' because that's where most discoveries end up," he said. "This valley, along with a lack of understanding of the basic processes at work in the disease, represent the main reasons that no one has yet developed a significant treatment for the disease. Douglas is taking us through this valley, allowing a completely new approach to enter clinical trials, which, if his goal for support is reached, should begin in the next two to three years."
Rosenberg established Sponsored Research Holdings, LLC (SRH) as the vehicle for funding the new therapeutics, an arrangement that could yield profits for his foundation and other venture philanthropists or investors joining his effort. Ideally, SRH will raise and invest up to $10 million to perform research and human proof of concept studies. SRH and Buck will participate together in any royalties and milestones that occur as a result of any licensing and/or commercialization created during the effort.
"Douglas's involvement is unique in the realm of biomedical research," said Brian Kennedy, PhD, the Buck Institute's Chief Executive Officer. "I know of no other individual who has committed to fund lead and pre-clinical drug development with the expressed intent of moving it specifically to human testing. His commitment and his business approach to this urgent need provide a new model for the research industry."
"I believe in what Dale is doing and will be extremely active in meeting the $10 million goal," said Rosenberg. "I've established different investment vehicles for this partnership to facilitate involvement from any organization or individual who's interested in supporting this work. A foundation can either make a grant or make a program related investment (PRI); an individual can make a donation and take the tax deduction or they can invest as if it were a straightforward venture deal. Either way we should have enough different buckets to attract the requisite funding."
Rosenberg says his father, who set high standards for how to give back to the world, has been a role model for this effort. "I recognize the odds are stacked against us, but as my dad always said, it's important to try. If I can inspire others to commit their dollars and time too, then I will have done a job to be proud of," said Rosenberg. "Best case scenario is we get a successful treatment for Alzheimer's in my lifetime. At the very least we can lead the research effort in a desperately needed new direction."
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