The Cryptic Rite Charitable Foundation Inc

Alzheimer’s Disease Research

 

My laboratory has been focused on the discovery of pathways that lead to Alzheimer’s disease progression and the discovery of potential therapeutic interventions. The donations from the Cryptic Rite Charitable Foundation have helped in the understanding of two potential therapeutic strategies to treat Alzheimer’s disease, as well as present studies aimed at identifying new treatment strategies.

 

The first therapy that we investigated was based on the attempt to vaccinate against Alzheimer’s disease, as is done with the Poliovirus or Rubella (German Measles), to prevent Alzheimer’s disease.  The target in the vaccination attempts was the toxic amyloid-beta peptide, which demonstrated efficacy in the mouse model of Alzheimer’s disease.  However, this proved harmful in clinical trials of AD patients resulting in unacceptable side-effects.  This strategy was not abandoned but modified from asking the body to generate an immune response to the amyloid-beta peptides to developing the antibodies in a laboratory that would function in a similar manner.  Our laboratory investigated the part of the protein that was crucial for benefit in the mouse model in the hope that targeting a specific part of the protein would have increased efficacy.  The verdict is still out on this type of therapy however many large pharmaceutical companies are continuing to pursue this strategy.

 

The second treatment strategy that we are investigating is a small molecule, scyllo-inositol, that binds to the toxic amyloid-beta protein and promotes clearance from the brain thus preventing memory loss.  We tested this compound in mouse models of Alzheimer’s disease and demonstrated that treatment could both prevent and treat existing cognitive and memory deficits.  We further confirmed that the memory benefits of this treatment resulted from clearance of the toxic proteins from the brain.  Scyllo-inositol underwent clinical trials for treatment of mild to moderate Alzheimer’s disease under the moniker, ELND005.  These trials failed to demonstrate memory and cognitive improvement in patients however it prevented the emergence of the neuropsychiatric symptoms normally associated with advancing disease.  In light of these results, scyllo-inositol is being tested in clinical trials for both Alzheimer’s disease and Down’s syndrome patients to control agitation and aggression.  The clinical trials are conducted by a multinational pharmaceutical company, ELAN Corporation Plc. 

 

The clinical trials preformed to date have taught the research community that the treatment of Alzheimer’s disease will likely require drugs that target more than one pathway that is damaged in the disease progression.  In light of this, our laboratory is presently trying to identify pathways that are rescued but most importantly that are not rescued after treatment with scyllo-inositol.  By identifying the pathways that are not rescued, we will identify new drug targets that can either be tested with existing drugs utilized in other diseases or for development of new drugs.