UPDATED: Intellect Neurosciences chases holy grail of Alzheimer's: a preventive vaccine

What's the focus of Alzheimer's disease vaccine research? Dr. Daniel Chain, Intellect Neurosciences' ($ILNS) chairman and CEO, gave FierceVaccines his thoughts: "A prophylactic vaccine would be the holy grail of Alzheimer's disease management--we could use it in anyone who might be at risk," says Chain.

So, how close are we to this goal, and what is Intellect Neurosciences' approach? First, a bit of history...

Alzheimer's disease immunotherapy has been around since the late 1990s with monoclonal antibodies specific to beta amyloid. There are a number of antibodies in the clinic, with the most advanced example of these being bapineuzumab, originally developed by Elan ($ELN) and Wyeth and now in Phase III clinical trials with Pfizer ($PFE) and Johnson & Johnson ($JNJ), which have licensed Intellect's underlying patents invented by Chain.  

The first vaccine developed for Alzheimer's disease was Elan's AN1792, which used a full-length synthetic form of beta amyloid protein, the protein found in the plaques in the brain in Alzheimer's disease. In clinical trials, this treatment cleared the plaques--however, there was no improvement in cognition or survival, and a Phase IIa trial was discontinued because some people involved in the trial developed aseptic meningitis as the result of an autoimmune response. The next generation of Alzheimer's disease vaccines used short peptide fragments designed to trigger a very specific response against the protein and not its precursor, which has roles in healthy tissue, and this will help avoid autoimmunity. Intellect Neurosciences is developing a vaccine using this approach, which has the additional advantage that it can be used to target more than one abnormal protein.

"We are developing active Alzheimer's disease vaccines using our RECALL-VAX platform, which uses small fragments of antigen combined with tetanus toxoid to trigger a strong and highly specific immune response, which is likely to have less side effects," says Chain. RECALL-VAX was invented by Chain's brother, Benjamin, to overcome the problems associated with AN1792.

The lead candidate--RV03--is a dual target vaccine composed of RV01, against beta amyloid, and RV02 against delta tau, and is in development for the prevention and treatment of Alzheimer's disease. Used singly, RV02 also has potential for the treatment of prefrontal dementias, a collection of neurodegenerative diseases caused by abnormal tau protein leading to the death of nerve cells. There has been debate over whether the beta amyloid or the tau protein is the most important in the development of Alzheimer's disease, but recently research has emerged that suggests that the two proteins act in concert to cause irreversible damage. Intellect is the first company to capitalize on this important new finding.

"There is a precedent for multi-epitope vaccines in infectious disease, and we are trying this route for Alzheimer's disease by developing a combined vaccine, comprised of chimeric peptides with truncated versions of both beta amyloid and tau. This would be a first in class approach because it would target the two earliest steps in Alzheimer's disease pathogenesis. This vaccine could be both prophylactic and therapeutic, and could also have potential in the treatment of traumatic brain injury," says Chain.

Chain predicts that this vaccine could be in the clinic in three years, pending further preclinical testing. However, this is still early-stage research, and much further development is still needed.

The company is also looking at vaccines targeted at other proteinopathies associated with abnormal protein folding, such as Huntington's disease and Parkinson's disease.  --Suzanne Elvidge (email)