April 14, 2005. A new approach to immunotherapy for Alzheimer disease (AD) took center stage Tuesday afternoon at the American Academy of Neurology meeting in Miami. Norman Relkin of Weill Cornell Medical College presented results of a pilot study showing that mental function improved in six of seven AD patients treated with an intravenous immunoglobulin (IVIG) antibody preparation.
IVIG, an FDA-approved purified immunoglobulin fraction from normal human donor blood, has a 30-year track record of safe use for the treatment of immune and inflammatory diseases. Relkin’s results, while preliminary, indicate that the preparation, which contains natural antibodies to amyloid-β (Aβ), warrants further study as a potential way to deliver a controlled immune attack on the peptide while potentially avoiding the immune toxicities that doomed clinical trials of Elan’s Aβ vaccine (see ARF related news story on the various forms of immunotherapy currently being developed for AD).
Relkin and his colleagues first considered the idea of passive immunization after they discovered that AD patients had lower levels of Aβ antibodies than do normal people of the same age. When they determined that the commercial IVIG preparation contained antibodies to amyloid-β, including the forms most toxic to brain cells, they decided to try the IVIG as a kind of antibody replacement therapy. In the phase I study, seven participants averaging 74 years old with mild to moderate AD received one to four IVIG infusions each month for 6 months. Follow-up included measurements of blood and CSF Aβ levels and cognitive testing. The researchers showed that blood levels of anti-Aβ antibodies increased after the infusion. More importantly, Relkin and colleagues measured a significant increase in plasma levels of Aβ, indicating that the peptide was being mobilized by the antibody treatment—the ability of peripheral antibodies to draw Aβ out of the brain was previously documented (see ARF related news story on the “peripheral sink” effect). No significant side effects were reported. These results echo a report last year from German researchers (Doda et al., 2004) who treated five patients with IVIG and saw a drop in Aβ in the CSF and an increase of the protein in the blood of those patients. In contrast to Relkin’s results, Doda and colleagues reported stabilization of cognitive decline, but no improvement in their patients.
In a press release, Relkin and senior investigator Marc Weksler called the results preliminary but “promising,” and said they provide a clear rationale for further development of IVIG for AD. Preparations for a phase II controlled trial in more patients are underway, according to the press release.—Pat McCaffrey.