Currently five drugs have received approval for treatment of Alzheimer's disease. Although no cure for Alzheimer's disease currently exists, these medications can help alleviate symptoms and slow progression. Trials continue for several other compounds, including those that directly impact the underlying causes of Alzheimer's disease and those that alleviate or slow symptoms.
Preventing the Formation of Beta-Amyloid
Some trials focus decreasing amounts of the protein beta-amyloid, which exists at high levels in the brains of people with Alzheimer's disease. These are more comprehensively reviewed by Judith Neugroschl and Mary Sano in the January 2010 edition of the "Mount Sinai Journal of Medicine," and by Martin Citron in the May 2010 edition of "Nature Reviews: Drug Discovery."
Drug studies targeting beta-amyloid take two main directions; the first stops its formation. To this end a drug called LY450139/semagacestat inhibits gamma-secretase, an enzyme involved in the production of beta-amyloid. As LY450139 was shown by Randall Bateman and colleagues in the July 2009 edition of "Annals of Neurology" to reduce brain levels of beta-amyloid in healthy subjects, further trials continue on people with Alzheimer's disease.
Clearing Already Formed Beta-Amyloid
Decreasing the amount of beta-amyloid may also include clearing what is already there. Studies here focus on drugs that stimulate the body to create antibodies against beta-amyloid or on direct injection of such antibodies. Using the first method, trials of a drug called AN-1792 found that those whose antibody levels were high after therapy had significantly lower functional decline compared to a placebo, as reported by Bruno Vellas and colleagues in the April 2009 edition of "Current Alzheimer Research." However, as in part of the AN-1792 trial six percent of the participants developed a dangerous brain inflammation.
The lessons learned from the AN-1792 trials were used to develop new compounds including antibodies named bapineuzumab, solanezumab and immunoglobulin G. Stephen Salloway and colleagues reported significant benefits of bapineuzumab on cognitive tests for some patients in the December 2009 edition of "Neurology." Only those who did not have a gene called APOE epsilon 4--which around 40 percent of those with late-onset Alzheimer's disease have--were tested. Trials for these compounds continue.
Other Breakthrough Medications
An antihistamine called latrepiridine or Dimebon proves another promising drug. While its mechanism of action is not fully understood, in a July 2008 study by Rachelle Doody of patients with mild to moderate Alzheimer's disease, published in "Lancet," at both 26 and 52 weeks participants had improved scores on cognitive performance, behavior and global function compared to the beginning of the study and to a placebo. However, trials by the drug company Pfizer have not yet confirmed these results.
The brains of people with Alzheimer's disease have another characteristic in the appearance of long strands of the protein tau that form 'neurofibrillary tangles' inside nerve cells. An agent called methylthioninium chloride, or methylene blue, directed at dissolving tau and preventing aggregation, was shown in trials over 24 and 50 weeks to significantly slow cognitive decline, as discussed by Charles Wischik and colleagues in the April 2009 edition of "The Journal of Nutrition, Health & Aging." Studies with this therapy continue.
References
- "Mount Sinai Journal of Medicine;" Current Treatment of Recent Clinical Research in Alzheimer's Disease; Judith Neugroschl and Mary Sano; January 2010
- "Nature Reviews: Drug Discovery;" Alzheimer's Disease: Strategies for Disease Modification; Martin Citron; May 2010
- "Annals of Neurology;" A Gamma-secretase Inhibitor Decreases Amyloid-beta Production in the Central Nervous System; Randall Bateman et al; July 2009
- "Current Alzheimer Research;" Long-term Follow-up of Patients Immunized with AN1792: Reduced Functional Decline in Antibody Responders; Bruno Vellas et al; April 2009
- "Neurology;" A Phase 2 Multiple Ascending Dose Trial of Bapineuzumab in Mild to Moderate Alzheimer Disease; Stephen Salloway et al; December 2009
