by Daniel B. Michael, M.D., Ph.D., Neurosurgeon at Michigan Head & Spine Institute
Everyone forgets, from the day we are born until we die. Memory is one of the most important functions our brains provide. When we forget or cannot recall an event, person or thing it can be frustrating. When such memories can never be recalled it can be life threatening. Alzheimer Disease (AD) is the progressive loss of certain types of memory due to specific degenerative changes in the brain. Twelve years following the diagnosis, over 95% of AD patients are dead. Alzheimer Disease is fatal and currently there is no effective treatment.
In 2012 there were 5.4 million estimated cases of AD with approximately 36 million cases worldwide. The incidence is expected to quadruple by 2050. In 2012 US the cost to care for AD patients was estimated to be $200 Billion; in 2050 the cost will increase to an estimated, $1.2 Trillion, 70% paid for by Medicare. Unless effective treatments for AD can be found we face an unprecedented healthcare crisis.
Dr. James Fontanesi, a noted radiation oncologist then on staff at William Beaumont Hospital (WBH), Royal Oak, MI, observed that relatively low doses of external radiation had been used to treat abnormal deposits of amyloid in parts of the body other than the brain. Amyloid deposition in the brain has been thought to play an important role in the development of AD. He hypothesized that radiation could be used to reduce amyloid in the brains of AD patients and lead to improved memory function.
Over the past five years Dr. Fontanesi gathered a team of radiation oncologists, radiobiologists, and behavioral psychologists to design and carry out animal laboratory studies to see if radiation would reduce amyloid in the brain, improve memory, and if so by what mechanisms this treatment worked. Daniel Michael, M.D., MHSI neurosurgeon and neuroscientist, was part of this team, providing help in experimental design and analysis. The MHSI board of directors voted to provide grant money to support this research.
The research used a transgenic mouse model of AD. Early experiments subjecting one half of the mouse’s brain to radiation demonstrated in dramatic fashion that amyloid could be reduce using this treatment (see figure). Subsequent studies suggested the best dose of radiation to use and possible mechanisms by which the radiation reduced amyloid. Whole brain radiation mouse studies then provided evidence that radiation improved memory in the AD mice. The results of these studies have been reported at radiation oncology, AD and neuroscience meetings worldwide.
In November 2015, the results of these experiments were reported in the peer reviewed journal, Radiotherapy and Oncology (Marples B, McGee M, Callan S, Bowen SE, Thibodeau BJ, Michael DB, Wilson GD, Maddens ME, Fontanesi J, Martinez AA: Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer’s Disease (AD). Radiother Oncol. 2015 Nov 23. pii: S0167-8140(15)00568-X. doi: 10.1016/j.radonc.2015.10.019. [Epub ahead of print] PMID: 26615717).
These animal studies have provided the basis for a Phase 1 human safety trial of radiation in AD patients. This trial has been developed in cooperation with the FDA. It is currently undergoing institutional review board scrutiny and is expected to enroll the first AD subjects in 2016. In addition to members of the team from Beaumont Hospitals and 21st Century Oncology, Mary Martin, RN, Dr. David Lustig, M.D., neurologist, and Dr. Michael all from MHSI will be participating in this exciting study.
MHSI is proud to continue its support of research which we hope will lead to an effective treatment for AD.