Vaccines

Older news items (pre-2010) brought over from the old website

Immunization with AB42 does not prevent dementia despite clearing associated brain plaques

Disappointingly, analysis of 80 Alzheimer's patients who had been involved in trialing immunisation against amyloid-β in September 2000, has found that, despite a lower level of amyloid-β plaques, there was no improved survival or increased time to severe dementia in those who were immunised.

Holmes, C. et al. 2008. Long-term effects of AB42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. The Lancet, 372 (9634), 216-223.

http://www.eurekalert.org/pub_releases/2008-07/l-iwa071608.php

Vaccine prevents Alzheimer's

A vaccine has successfully prevented the development of amyloid plaques and tau tangles in the brains of genetically engineered mice. The vaccinated mice also demonstrated normal learning skills and functioning memory. There were no major side-effects. Human trials are still a few years off.

Frazer, M.E. et al. 2008. Reduced Pathology and Improved Behavioral Performance in Alzheimer's Disease Mice Vaccinated With HSV Amplicons Expressing Amyloid-β and Interleukin-4. Molecular Therapy, 16, 845-853.

http://www.eurekalert.org/pub_releases/2008-05/uorm-vti051908.php

Alzheimer's vaccine clears plaque but doesn't improve memory

A two-year canine study has revealed that although a promising vaccine being tested for Alzheimer's disease clears beta-amyloid plaques from the brain, it doesn’t seem to help restore lost learning and memory abilities. Autopsies showed that although plaques had been cleared from multiple brain regions, damaged neurons remained. The findings suggest that simply treating beta-amyloid plaques may have only limited clinical benefit if started after there is significant plaque growth, and a combination of vaccination with other therapies aimed at repairing damaged neurons may be best.

Head, E. et al. 2008. A Two-Year Study with Fibrillar β-Amyloid (Aβ) Immunization in Aged Canines: Effects on Cognitive Function and Brain Aβ. Journal of Neuroscience, 28, 3555-3566.

http://www.eurekalert.org/pub_releases/2008-04/uoc--avc040408.php

Transdermal vaccine effective in treating Alzheimer's disease in mice

Previous research on an Alzheimer's vaccine proven safe and effective in an animal model was suspended when the initial clinical trial caused brain inflammation and death in a small percentage of patients. A new mouse study has now had success with a transdermal method of delivery (a skin patch), that doesn’t appear to trigger the toxic reaction of past immunization strategies. Further research is needed to assess whether the transdermal vaccine can curb memory loss as well as reduce Ab plaque.

Nikolic, W.V. et al. 2007. Transcutaneous -amyloid deposits without T cell infiltration and microhemorrhage. Proceedings of the National Academy of Sciences, 104 (7), 2507-2512.

http://www.eurekalert.org/pub_releases/2007-01/uosf-tve011807.php

Hopeful results from interrupted Alzheimer's vaccine study

Phase 2 of a human clinical trial vaccinating patients with beta-amyloid was halted in 2002 when some participants developed brain inflammation. Participants continued to be monitored, however, and results show that participants whose immune systems mounted a response against beta amyloid performed significantly better on a series of memory tests than those who received a placebo injection (but not on 5 tests often used to diagnose dementia). There were also signs of reduced levels of tau protein (a protein considered a sign of cell death) in those who had an immune response. As a result, new trials are underway, this time using humanized antibodies rather than beta amyloid itself. The antibodies should help trigger the immune system to attack beta amyloid, but will be cleared by the body soon after injection.

Gilman, S., Koller, M., Black, R.S., Jenkins, L., Griffith, S.G., Fox, N.C., Eisner, L., Kirby, L., Boada Rovira, M., Forette, F. & Orgogozo, J-M. for the AN1792(QS-21)-201 Study Team. 2005. Clinical effects of Aß immunization (AN1792) in patients with AD in an interrupted trial. Neurology, 64, 1553-1562.

Fox, N.C., Black, R.S., Gilman, S., Rossor, M.N., Griffith, S.G., Jenkins, L. & Koller, M. for the AN1792(QS-21)-201 Study Team. Effects of Aß immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology, 64, 1563-1572.

http://www.eurekalert.org/pub_releases/2005-05/uomh-hrf050505.php

Progress on Alzheimer's vaccine

Efforts to create a vaccine for Alzheimer’s have been hindered by potential side effects — some human participants in an earlier trial developed severe inflammation in the brain. A mouse study has now substantially increased the safety of the vaccine by including a tetanus toxin to alter the immune response. Future studies are planned using the herpes virus.

Bowers, W.J., Mastrangelo, M.A., Stanley, H.A., Casey, A.E., Milo, L.J.Jr. & Federoff, H.J. 2004. HSV amplicon-mediated Ab vaccination in Tg2576 mice: differential antigen-specific immune responses. Neurobiology of Aging, available online 25 June 2004.

http://www.eurekalert.org/pub_releases/2004-06/uorm-hta062904.php

Mice immunized against Alzheimer's

Using a new vaccine, NYU School of Medicine researchers have prevented the development of Alzheimer's disease in mice genetically engineered with the human gene for the disease. The researchers are optimistic that this new vaccine is safer than one already being tested in early human clinical trials. The new vaccine, modeled on a fragment of a protein called amyloid, which is most frequently implicated in causing Alzheimer's, reduced the amount of amyloid plaque in the brains of mice by 89 percent. At the same time, the vaccine reduced the amount of soluble amyloid beta in the brain by 57 percent. Early clinical trials of the new vaccine could begin within one year.

Sigurdsson, E. M., Scholtzova, H., Mehta, P. D., Frangione, B., & Wisniewski, T. (2001). Immunization with a Nontoxic/Nonfibrillar Amyloid-β Homologous Peptide Reduces Alzheimer’s Disease-Associated Pathology in Transgenic Mice. The American Journal of Pathology, 159(2), 439–447. doi:10.1016/S0002-9440(10)61715-4

http://www.eurekalert.org/pub_releases/2001-08/nyum-nrs080101.php

A vaccine for Alzheimer's

A vaccine may help prevent and treat the disabling memory loss and cognitive impairment of Alzheimer's disease. Alzheimer's occurs when amyloid-beta peptides accumulate in the brain, forming plaque. While previous studies have shown that vaccinating mutated mice with this amyloid-beta peptide could remove the plaque deposits, there was never any evidence of improvement in brain function, until now. The researchers also believe this study provides the final element of proof that Alzheimer's is initiated by amyloid-beta peptides. The researchers believe clinical trials could begin on human subjects within the year.

Johnson, J. D., McDuff, S. G. R., Rugg, M. D., & Norman, K. A. (2009). Recollection, Familiarity, and Cortical Reinstatement: A Multivoxel Pattern Analysis. Neuron, 63(5), 697–708. doi:10.1016/j.neuron.2009.08.011

http://www.eurekalert.org/pub_releases/2000-12/UoT-UoTr-1912100.php