re Rx: Dedicated to exploring, informing and reflecting on the world of repurposing research
Dr. Teresa McNally, January 16, 2014
The National Alzheimers Project Act (NAPA) calls for a concerted national plan for Alzheimer’s Disease and Related Dementia (ADRD) treatment and care. This collaboration between multiple federal healthcare offices, industry and non-profits is tasked to (a) prevent and treat ADRD by 2025, (b) optimize the quality and efficiency of care, (c) expand support for patients and their families, (d) enhance awareness and engagement, (e) track progress of the plan and to improve the process. The plan and its goal will also be mirrored by the G8 countries making this a global effort to develop treatments for ADRD.
The aggressive time-line highlights drug repurposing as a major milestone in the primary objective, to treat and prevent ADRD by 2025. This year, experts from the pharmaceutical industry, government, academia, FDA and the non-profit sector will convene to select at least 6 drugs suitable for repurposing or combination therapy. These will be identified based on evidence that they modulate disease relevant pathways/networks, show preclinical efficacy in relevant model systems, modulate biomarkers of target engagement in humans and are safe in the intended target population. Compounds that meet these criteria will move forward into phase II and phase III clinical trials to demonstrate efficacy in humans by the 2025 deadline.
Every 68 seconds, someone in the USA develops ADRD. The 5.2 million sufferers create an anual national care cost of over 206 billion dollars. As the US population continues to age, 13.2 million patients are predicted by 2025. There are no disease modifying therapies. Although 5 FDA approved drugs improve symptoms for a short time in some cases, they have no impact on survival or neuronal degeneration.
Research suggests a link between Alzheimer’s disease and type II diabetes, another common disease in the elderly. Alzheimer’s patients often have impaired glucose tolerance, a hallmark of diabetes. Diabetics show cognitive dysfunctions like those that precede ADRD. Based on positive findings in mice, NovoNordisk will initiate a clinical trial to repurpose their anti-diabetes drug, liraglutide, for ADRD (8). They will evaluate the effect of the drug on cerebral blood flow, plaque deposition, glucose uptake and cognitive function after 6 months of treatment. Other agents being repurposed for ADRD include the retinoic receptor agonist tamibarotene, a drug approved for treatment for promyelocytic leukemia in Japan. This compound showed a promising reduction in plaque deposition in brains of ADRD transgenic mice (10) and is now in human clinical trials.
The NAPA act has initiated a global collaborative effort to develop much needed therapies for one of the largest areas of unmet medical need in modern times. With clinical trials to repurpose existing therapies already underway, this global plan will increase the likelihood of a successful outcome and develop a framework for future repurposing efforts in other therapeutic areas.