Amyloid beta immunotherapy

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The beta-amyloid immunotherapy is an experimental therapeutic approach for the treatment of Alzheimer's disease . Colloquially it is often called Alzheimer's vaccination . However, it is not a process that is directed against pathogens of an infectious disease like a vaccination .

background

As part of the therapeutic approach, it is assumed that active or passive immunization against the protein beta-amyloid , the component of the senile plaques typical of the disease, can slow down the progression of the disease. Indeed, in a mouse model of Alzheimer's disease, active immunization with beta-amyloid (Abeta42) prevented the development of neuritic plaques in young animals. In older animals, the extent of the neuropathological changes was at least reduced. Since improvements in learning behavior and memory performance could also be achieved after such an immunization in mouse models, great hopes were directed towards the possible transferability of these animal experiment results to humans.

Use in humans

Initial clinical studies initiated by Elan Corporation , the manufacturer of a synthetic variant of beta-amyloid ( AN-1792 ) that was used for immunization, had to be discontinued due to serious, sometimes fatal side effects. The neuropathological examination of the brains of deceased study participants showed that the immunization had triggered inflammation of the brain and meninges ( meningoencephalitis ). Nonetheless, a significant reduction in plaques in certain brain regions could also be demonstrated in humans. This finding suggests that beta-amyloid immunotherapy could potentially play a role in Alzheimer's disease if the serious side effects could be avoided. The development of new experimental immunization strategies has therefore remained an important subject of research. Under the name Bapineuzumab companies have Wyeth and Elan Corporation, a anti-beta-amyloid monoclonal antibody developed. The effectiveness of bapineuzumab is currently being investigated in the USA as part of a clinical study in patients with the onset of symptoms of Alzheimer's disease. US companies Johnson & Johnson and Pfizer announced that they are discontinuing clinical development of the Alzheimer's drug bapineuzumab. The monoclonal antibody, which was supposed to remove the beta-amyloids from the brains of dementia patients, did not meet expectations in a second phase III study either.

literature

Individual evidence

  1. ^ Boche & Nicoll: The role of the immune system in clearance of abeta from the brain. In: Brain Pathol . 2008; 18 (2): 267-78. PMID 18363937 (review article)
  2. ↑ Schen et al .: Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. In: Nature . 1999; 400 (6740): 173-7. PMID 10408445
  3. ↑ Younkin: amyloid beta vaccination: reduced plaques and improved cognition. In: Nat Med . 2001; 7 (1): 18-9. PMID 11135604
  4. ↑ Janus et al .: A beta peptide immunization reduces behavioral impairment and plaques in a model of Alzheimer's disease. In: Nature . 2000; 408 (6815): 979-82. PMID 11140685
  5. ^ Ingram: Vaccine development for Alzheimer's disease: a shot of good news. In: Trends Neurosci . 2001; 24 (6): 305-7. PMID 11356488
  6. ↑ Koch: Alzheimer: The beautiful dream of the vaccine. In: Dtsch Arztebl , 2000; 97 (30): A-2001 full text
  7. ↑ Schenk: Amyloid-beta immunotherapy for Alzheimer's disease: the end of the beginning. In: Nat Rev Neurosci . 2002; 3 (10): 824-8. PMID 12360327
  8. ↑ Nicoll et al .: Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. In: Nat Med . 2003; 9 (4): 448-52. PMID 12640446
  9. ^ Hawkes & McLaurin: Immunotherapy as treatment for Alzheimer's disease. In: Expert Rev Neurother . 2007; 7 (11): 1535-48. PMID 17997702 (review article)
  10. ↑ Simm: Alzheimer's disease: vaccination slows down memory deterioration. In: Dtsch Arztebl 2003; 100 (25): A-1718 full text (critical summary of the results of the clinical studies)
  11. ↑ NCT00574132 (study description at clinicaltrials.gov)
  12. ↑ Alzheimer's: Second study on antibody therapy canceled Deutsches Ärzteblatt , August 7, 2012. Retrieved on August 12, 2012.