Advances in Basic Research

Guy S. Eakin, Ph.D. Vice President Scientific Affairs American Health Assistance Foundation

Visit us at www.ahaf.org 1 (800) 437 2423

American Health Assistance Foundation www.ahaf.org

Research and educational programs covering: Alzheimers Disease Macular Degeneration Glaucoma Swanson and Bota, PNAS 2010

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American Health Assistance Foundation www.ahaf.org

Research and educational programs covering: Alzheimers Disease Macular Degeneration Glaucoma http://www.cccmkc.edu.hk/~kei-kph

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Visit us at www.ahaf.org 1 (800) 437 2423

General topic outline

1.

Recent advances in, and the role of, basic research (absent causes and prevention, genetics, ADNI, clinical trials) Non-neuroimaging approaches to early diagnosis a. b. CSF and serum tests, Neuro-psych approaches to diagnosis

2.

3. 4.

Pre-clinical drug development and discovery Traumatic brain injury

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General topic outline

1. Recent advances in, and the role of, basic research (avoiding causes and prevention, genetics, ADNI, genetics, clinical trials) 1. Role of Basic Research 2. The Basics of Basic Research in AD 3. Hot Topics. Non-neuroimaging approaches to early diagnosis a. b. 3. CSF and serum tests, Neuro-psych approaches to diagnosis

2.

Pre-clinical drug development and discovery

4.

Traumatic brain injury

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Role of Basic Science

Categories of research goals
Basic Research into fundamental principles of science or disease. Translational Clinical Determinations of safety and efficacy of drugs for human use How well does it work? Is it safe?

Research designed to transition basic research to clinical interventions.

Can it be manipulated or fixed in humans?

How does it work? What might be going wrong?

Other Translational
What refinements and cost effectiveness will predict acceptance by clinicians, insurers, etc? What policy and best practices research can assure maximal reach of any therapy?

Role of Basic Science

(vis vis the drug pipeline)

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Role of Basic Science

Visit us at www.ahaf.org 1 (800) 437 2423

Role of Basic Science

Visit us at www.ahaf.org 1 (800) 437 2423

Role of Basic Science

Visit us at www.ahaf.org 1 (800) 437 2423

General topic outline

1. Recent advances in, and the role of, basic research (avoiding causes and prevention, genetics, ADNI, genetics, clinical trials) 1. Role of Basic Research 2. The Basics of Basic Research in AD: What is a plaque and tangle oligomers? 3. Hot topics Non-neuroimaging approaches to early diagnosis a. b. 3. 4. CSF and serum tests, Neuro-psych approaches to diagnosis

2.

Pre-clinical drug development and discovery Traumatic brain injury

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What are the plaques and tangles?

http://www.nia.nih.gov/sites/default/files/nia-ad-image08_large.jpg

What are the plaques and tangles?

LaFerla and Querfrurth, NEJM 2010

Amyloid Plaques vs Oligomers

(Is amyloid acting as a big bomb or as itty bitty bullets)

Researchers created oligomer only mice (no, or few plaques) showed similar impairment to standard models but without presence of the plaques! If a gene that restores plaques is added back to the oligomer only mice: no further impairment is noted. Implications for plaque buster drugs

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What are the plaques and tangles?

http://www.nia.nih.gov/sites/default/files/nia-ad-image08_large.jpg

General topic outline

1. Recent advances in, and the role of, basic research (avoiding causes and prevention, genetics, ADNI, genetics, clinical trials) 1. Role of Basic Research 2. The Basics of Basic Research in AD: 3. Hot topics Amyloid Aggregation Tau Spreading Non-neuroimaging approaches to early diagnosis a. b. 3. 4. CSF and serum tests, Neuro-psych approaches to diagnosis

2.

Pre-clinical drug development and discovery Traumatic brain injury

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Amyloid Aggregation

http://www.alz.org/research/diagnostic_criteria/preclinical_recommendations.pdf

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Amyloid Aggregation

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Tau Spreading
(and the challenges of the word infectious)

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Tau Spreading
(and the challenges of the word infectious)

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General topic outline

1. Recent advances in, and the role of, basic research (avoiding causes and prevention, genetics, ADNI, genetics, clinical trials) 1. Role of Basic Research 2. The Basics of Basic Research in AD: 3. Hot topics Non-neuroimaging approaches to early diagnosis a. b. 3. 4. CSF and serum tests, Neuro-psych approaches to diagnosis

2.

Pre-clinical drug development and discovery Traumatic brain injury

Visit us at www.ahaf.org 1 (800) 437 2423

CSF measurements

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CSF measurements

For Sporadic (Late onset) AD: Clearance, but not production of Abeta differs between AD patients and controls

(Early onset and Downs syndrome is a different story)

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CSF measurements

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Blood ABeta measurements

(Less invasive, more uncertain) Meta analysis of 13 studies / >10,000 patients
AB42 levels or AB40 levels not predictive Lower AB42:AB40 ratio had 1.67 risk ratio (increased risk)

"Despite the limitations of existing research and heterogeneity across the studies considered, this systematic review and meta-analysis suggests that the ratio of plasma A42:A40 may have value in predicting the risk for later development of dementia or AD and merits further investigation,"

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Individual Diagnosis or Populations risk

(whats good for what?)

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General topic outline

1. Recent advances in, and the role of, basic research (avoiding causes and prevention, genetics, ADNI, genetics, clinical trials) 1. Role of Basic Research 2. The Basics of Basic Research in AD: 3. Hot topics Non-neuroimaging approaches to early diagnosis a. b. 3. 4. CSF and serum tests, Neuro-psych approaches to diagnosis

2.

Pre-clinical drug development and discovery Traumatic brain injury

Visit us at www.ahaf.org 1 (800) 437 2423

Preclinical Drug Development and Discovery

Visit us at www.ahaf.org 1 (800) 437 2423

Preclinical Drug Development and Discovery

Visit us at www.ahaf.org 1 (800) 437 2423

Preclinical Drug Development and Discovery

Visit us at www.ahaf.org 1 (800) 437 2423

Preclinical Drug Development and Discovery

repurposing old drugs: bexarotene preclinical studies

http://www.dementiatoday.com/?p=20584

Visit us at www.ahaf.org 1 (800) 437 2423

Preclinical Drug Development and Discovery

Visit us at www.ahaf.org 1 (800) 437 2423

General topic outline

1. Recent advances in, and the role of, basic research (avoiding causes and prevention, genetics, ADNI, genetics, clinical trials) 1. Role of Basic Research 2. The Basics of Basic Research in AD: 3. Hot topics Non-neuroimaging approaches to early diagnosis a. b. 3. 4. CSF and serum tests, Neuro-psych approaches to diagnosis

2.

Pre-clinical drug development and discovery Traumatic brain injury

Visit us at www.ahaf.org 1 (800) 437 2423

Traumatic Brain Injury

TBI patients show increased amyloid and tau deposition

Especially if the patient caries one or more APOE4 allele

And these APOE4 carriers are more susceptible (2 times as likely) to have poor outcomes following TBI

Pig TBI was used to show that amyloid deposition followed TBI, rather than
preceded.

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Thank you. Keep in touch!

Guy S. Eakin, Ph.D. geakin@ahaf.org Vice President Scientific Affairs American Health Assistance Foundation

Visit us at www.ahaf.org 1 (800) 437 2423