Combining Medications to Successfully Treat Alzheimer’s Disease
Everyone has had the experience of treating a cold. We typically take medications to
treat the symptoms. As the commercials inform us, these medications treat the runny nose, congestion, cough, and fever associated with the common cold. These medications help us feel better, but we all recognize that none of the medications will "cure" the cold. Fortunately our immune systems take care of this. But we also recognize that there is benefit to treating the symptoms of the cold. Simply put, we feel better.
In some respects, current treatment for Alzheimer's disease (AD) is similar to treating the symptoms of a cold. These treatments can help with the symptoms including memory loss, decline in function, and changes in mood and behavior. They do not, however, have any effect on the underlying cause of the disease.
Alzheimer's disease is a brain disease. At the most fundamental level, the symptoms of Alzheimer's disease are caused by the progressive loss of brain cells or neurons. As these brain cells are lost, so are the corresponding cognitive abilities such as memory and reasoning. The currently approved medications (Aricept, Exelon, Razadyne, Namenda) all help treat the symptoms of the disease. But there is no evidence that any of these medications stop the loss of brain cells.
Brain cells communicate with each other by releasing chemicals called neurotransmitters. As brain cells are lost, they lose the ability to release these transmitters. The currently approved AD medications, the "symptomatic drugs," boost the levels of these transmitters in the brain and in doing so help patients with function. But at the same time, there is the continuing loss of brain cells. Eventually, the loss of brain cells will overwhelm the ability of symptomatic drugs to boost functioning.
Enter the newest class of treatment for Alzheimer's disease - disease modifying drugs (sometimes called mechanism based drugs). This class of drugs is aimed at slowing and perhaps even eventually halting the loss brain cells. There are multiple approaches to developing disease modifying drugs. The most prominent approach is drugs and vaccines that effect beta amyloid. Amyloid is a sticky protein that in certain forms (Beta amyloid) kills brain cells. New therapies including the AD vaccine (see last month's post on immunotherapy for Alzheimer's), secretase inhibitors, and SALAs (selective amyloid lowering agents) are all aimed at preventing the formation or removing amyloid plaques. These and other drugs aimed at protecting neurons from the ravages of amyloid are currently in clinical trials.
It is likely that the combination of symptomatic and disease modifying drugs will provide the best benefit. In our clinic, we routinely combine cholinesterase inhibitors (Aricept, Exelon or Razadyne) with Namenda for some patients. Clinical research studies indicate that these combinations provide more benefit than either drug alone. In the future we are likely to combine multiple symptomatic drugs in a "cocktail," much like AIDS is currently treated. Combined with these "symptomatic cocktails" will be one or more disease modifying drugs/vaccines. The approach of combination therapy is already available to patients participating in clinical research trials. For example, patient taking a cholinesterase inhibitor plus Namenda are eligible to enter the ongoing vaccine trials.
These clinical research studies signal what treatment might be in the near future.