Elan Corp PLC (ELN): Elan's targeted AD genotypes in aab-001...

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Monday, 10/29/2007 1:40:55 PM

Monday, October 29, 2007 1:40:55 PM

Elan's targeted AD genotypes in aab-001 program:

From slides shown at the Alzheimer's Society's annual event entitled "Competing Paradigms in Alzheimer's Research", specifically a presentation from the Harvard Medical School, this data discusses the APOE genotypes.

Note that in Elan's pivotal trial program, the sub-populations (which amount to different disease indications, as they will have separate trials) are determined by whether or not they carry the 'APOE-e4 allele'.

APOE-e4 is risk factor for late-onset AD

•APOE - AD candidate gene on chromosome 19 - binds Ab in CSF.

•3 APOE variants (prevalence):

-APOE-e2 ~2% - protective (with e3)

-APOE-e3 ~75% - neutral

-APOE-e4 ~20%; >50% in AD - risk

•One e4 allele increases risk >3-fold.

•Two e4 alleles increase risk >10-fold.

•e4 risk strongest between 60-70 yr

How many more AD genes are there?

*Twin studies indicate that at least 80% of AD is inherited.

*The known early-onset familial AD gene mutations in APP, PSEN1, and PSEN2 account for only 1-2% of all AD.

*APOE-e4 acts an inherited risk variant in roughly 50% of late-onset sporadic AD cases.

*APOE-e4 likely requires other inherited risk variants and environmental factors to trigger AD.

*Roughly 70% of AD genetics remains unsolved.

"....on the biotech battle-field, you need some élan...."