Two years ago Car Talk, one of the most popular shows on National Public Radio, ended after 35 years on the air. Alzheimer’s disease (AD) was to blame. Co-host Tom Magliozzi had progressive symptoms associated with the disease that affected his sharp wit and jovial banter that the show is famous for. Car Talk’s longtime executive producer Doug Berman in a recent interview with Terri Gross on NPRs Fresh Air explained why the show ended. “He [Tom] felt that he just wasn’t what he used to be,” Berman said. “And he had such an incredible mind that it was really difficult for him.”

Car Talk brothers Tom and Ray Magliozzi. (Image source abcnews).

Car Talk brothers Tom and Ray Magliozzi. (Image source abcnews).

Sadly, Tom Magliozzi recently passed away from complications related to Alzheimer’s. It’s a cruel disease that robs people of their memory and causes dementia as the disease progresses. AD affects as many as 5.1 million people in the US alone and the number will only rise with our growing elderly population. There are a few FDA approved drugs for the treatment of AD symptoms. However, there are no cures or existing therapies that stop disease progression. The Buck Institute hopes to change this predicament with a new therapeutic treatment for patients with early stages of Alzheimer’s.

While a majority of the work done at our Institute is preclinical, this week the Buck launched its first clinical trail in Australia to treat amnestic mild cognitive impairment (aMCI), a disease in which 10-15% of affected individuals progress to AD each year. The first subject was recently enrolled in a phase Ib/IIa study to test the safety, tolerability, and efficacy of two doses of the drug F03. F03 is already clinically approved for other disease indications in multiple countries, and the Buck’s study hopes to provide evidence of its safety and efficacy in a group of patients with aMCI. If F03 shows promise in the current clinical trial, the hope is to perform a much larger and more extensive trial in the US and Australia, which would enable FDA approval if the drug succeeds.

Dr. Dale Bredesen, Professor at the Buck Institute.

Dr. Dale Bredesen, Professor at the Buck Institute.

F03 was identified as a promising drug to treat aMCI in Dr. Dale Bredesen’s lab at the Buck. Dr. Bredesen discovered that F03 improves cognitive function and reduces memory loss in multiple mouse models of AD. A major cause of Alzheimer’s and the cognitive complications associated with it is believed to be the accumulation of plaques in the brain that are enriched in β-amyloid (Aβ), a peptide formed from the breakdown of amyloid precursor protein (APP). F03 breaks down APP into peptides that are less harmful than Aβ. Importantly, the mechanism by which F03 targets APP is different than the current drugs used to treat early stage AD symptoms (such as aMCI). These existing drugs function by increasing the amount of the neurotransmitter acetylcholine in the brain through inhibition of the enzyme Cholinesterase. However, anticholinesterase inhibitors can produce significant side effects in some patients and vary in efficacy from individual to individual. Dr. Bredesen and his lab hope that F03 can address limitations and overcome the drawbacks of these current drugs used to treat AD.

As a postdoc at the Buck, it is exciting to see the research we conduct at the bench translate to patient’s bedsides.  It certainly adds a big-picture perspective to our daily work of teasing out the biological mechanisms of aging and age-related diseases and how to manipulate these mechanisms through environmental or pharmacological interventions. We are inspired by our Institute’s efforts to address unmet clinical needs in the field of Alzheimer’s disease, and we will strive to make sure that the next clinical trial produced from our research is sooner rather than later.

For more on The Buck Institutes first clinical trial read The Buck Institute’s recent press release.