Sharp Brains: Brain Fitness and Cognitive Health News

Neuroplasticity, Brain Fitness and Cognitive Health News

Icon

The State of Personalized Medicine: The Role of Biomarkers

(Editor’s Note: this is Part 1 of the new 3-part series writ­ten by Dr. Evian Gor­don draw­ing from his par­tic­i­pa­tion at the Per­son­al­ized Med­i­cine World Con­gress on Jan­u­ary, 23, 2012 at Stan­ford Uni­ver­si­ty.)

On aver­age, the med­ica­tions pre­scribed for brain-relat­ed con­di­tions ben­e­fit approx­i­mate­ly 50% of patients. But which 50%?

Per­son­al­ized Med­i­cine seeks to move away from the cur­rent “1 size fits all, tri­al and error” approach that has been nec­es­sary because of a lack of evi­dence. Instead, it focus­es on match­ing the bio­log­i­cal char­ac­ter­is­tics of each per­son with the best med­ica­tion and dose for them. Tests that mea­sure these char­ac­ter­is­tics are called “bio­mark­ers”.

The bot­tom line of Per­son­al­ized Med­i­cine is to improve out­comes that mat­ter to both the doc­tor and the patient, and reduce the cur­rent costs. So far, the focus of Per­son­al­ized Med­i­cine has been in can­cer and some chron­ic med­ical con­di­tions. It is new to con­di­tions of brain health and to psy­chi­a­try.

Per­son­al­ized Med­i­cine is being dri­ven by the FDA (Fed­er­al Drug Admin­is­tra­tion in Wash­ing­ton) and is being adopt­ed to dif­fer­ent extents, by the stake­hold­er groups we will out­line in the third and final part of this series.

With the com­ple­tion of the Genome Project in 2003, expec­ta­tions were high that genet­ic vari­ants would help objec­tive­ly deter­mine diag­nos­tic cat­e­gories and pre­dict indi­vid­u­al­ized treat­ment response. But Genomics (“Pan-omics”) of the grow­ing num­ber of mol­e­c­u­lar mea­sures (Genes [DNA], Gene Expres­sion [RNA], Pro­teomics and Metabolomics) have to some extent “over­promised and under-deliv­ered”. This is espe­cial­ly true in Psy­chi­a­try where the con­di­tions we are tack­ling involve a com­plex com­bi­na­tion of genet­ics and gene-expe­ri­ence inter­ac­tions.

But, oth­er med­ical con­di­tions are also com­plex, and involve gene-expe­ri­ence inter­ac­tions. Accord­ing to the Per­son­al­ized Med­i­cine Coali­tion (PMC) in Wash­ing­ton, there were 13 exam­ples of Per­son­al­ized Med­i­cine diag­nos­tic Bio­mark­ers and med­ica­tions in 2006 and 72 in 2011.

Spe­cif­ic out­comes in Can­cer are promis­ing for the devel­op­ment of Per­son­al­ized Med­i­cine in Psy­chi­a­try. Some exem­plar suc­cess­es are out­lined below.

Per­son­al­ized Med­i­cine Suc­cess­es in Med­i­cine

Select­ed Exam­ples of Per­son­al­ized Med­i­cine Bio­mark­ers in Can­cer:

  • Her­ceptin ® (trastuzum­ab) treat­ment – is iden­ti­fied by the HER-2/neu recep­tor – and is used in Breast can­cer: about 30% of can­cers have an over-expres­sion of HER-2 pro­tein, which respond to Her­ceptin.
  • Gleevec ® (Ima­tinib mesy­late) – is iden­ti­fied via BCR-ABL – and used to treat Chron­ic Myloid Leukemia: increas­es life expectan­cy from 5% — 95% at 5 years.
  • Zelb­o­raf ®(Vemu­rafenib) – is iden­ti­fied by BRAFV600E – and used to treat Melanoma, where the late stage prog­no­sis is poor: 60% of patient have a defect in their DNA and the drug only ben­e­fits those with the V600E defect.
  • Oth­er suc­cess­ful Per­son­al­ized Med­i­cine exam­ples of “Treat­ment – Bio­mark­er” com­bi­na­tions are in Colon Can­cer (Erbitux – EFGR), and Lung Can­cer (Xalko­ri – ALK).

There are also exam­ples of Bio­mark­ers that are not spe­cif­ic to 1 drug, but affect the metab­o­lism in the liv­er of many drugs, with effects on dosage. The best known exam­ple is the CYP 450 enzyme and its appli­ca­tion to Coumadin War­farin). PGx® Pre­dicts the CYP2C9 enzyme, which in car­dio­vas­cu­lar dis­ease pre­dicts the like­li­hood of adverse events with War­farin ther­a­py. The Amplichip® CYP2D6 is linked to approx­i­mate­ly 25% of all Psy­chi­atric drugs pre­scribed and can be used to avoid dose ‘tox­i­c­i­ty’ and pos­si­ble adverse events in indi­vid­u­als who are high metab­o­liz­ers.

*Per­son­al­ized Med­i­cine Mol­e­c­u­lar Tests rec­om­mend­ed by the FDA are list­ed on the FDA’s web­site Here.

The Per­son­al­ized Med­i­cine Coali­tion (web­site here) pro­vides an excep­tion­al ongo­ing sum­ma­ry of new Bio­mark­ers in Per­son­al­ized Med­i­cine.

The extent of the ben­e­fits of real world exam­ples of Per­son­al­ized Med­i­cine are grow­ing. I list three exam­ples below.

Dr Shankaran found that $604 mill could be saved per annum if Vectibix and Erbitux med­ica­tion for metasta­t­ic Col­orec­tal can­cer was restrict­ed to patients whose KRAS gene was not mutat­ed, since only they would be the patients like­ly to ben­e­fit (more here).

Dr Bark­er (for­mer Deputy Direc­tor of the Nation­al Can­cer Insti­tute) report­ed that can­cer fatal­i­ties have declined by 22% in men and 14% in women over the past 40 years, thanks in part to Per­son­al­ized Ther­a­pies such as Glee­vac and Tarce­va.

A real world exam­ple of CYP is the pre­dic­tion that cor­rect per­son­al­ized dos­ing of War­farin could pre­vent 17,000 strokes in the U.S. and avoid 43,000 emer­gency room vis­its. The Mayo Clin­ic and Med­co test­ed this pre­dic­tion in 3,600 patients and found hos­pi­tal­iza­tions for heart rate patents were reduced by 30% (Epstein RS et al. J Amer­i­can Col­lege Car­di­ol­o­gy. 55:2804–12. 2010).

In con­trast to these suc­cess­es, most Per­son­al­ized Med­i­cine research in Psy­chi­a­try using mol­e­c­u­lar mea­sures alone have failed to repli­cate. Whilst dis­ap­point­ing, this is not sur­pris­ing, since 80% of human 25,000 genes have some effect on the brain.

To Be Con­tin­ued…

New Series on Per­son­al­ized Med­i­cine and the Brain:

  • Mon­day, Feb­ru­ary 13th: The State of Per­son­al­ized Med­i­cine (above)
  • Mon­day, Feb­ru­ary 20th: Chal­lenges and Oppor­tu­ni­ties of Per­son­al­ized Med­i­cine in Psy­chi­a­try
  • Mon­day, Feb­ru­ary 27th: Work­ing with Health Care Indus­try Stake­hold­ers Towards Brain-based Per­son­al­ized Med­i­cine
– Dr Evian Gor­don is the Exec­u­tive Chair­man of the Brain Resource Com­pa­ny.  He ini­tial­ly drew upon  his sci­ence and med­ical back­ground to estab­lish the inter­dis­ci­pli­nary Brain Dynam­ics Cen­ter, in 1986.  Through the Brain Dynam­ics Cen­ter and its col­lab­o­ra­tive net­works, Dr Gor­don estab­lished an “inte­gra­tive neu­ro­science” approach, ground­ed in the use of stan­dard­ized meth­ods across mul­ti­ple types of data. Using this approach, Dr Gor­don found­ed the “Brain Resource Com­pa­ny”, that cre­at­ed the first inter­na­tion­al data­base on the human brain. The data­base is the asset which under­pins the devel­op­ment of new tools for brain health and its per­son­al­ized appli­ca­tion in the mar­ket, such as assess­ments of brain health, deci­sion sup­port sys­tems, and per­son­al­ized train­ing pro­grams. Brain Resource has also sup­port­ed the for­ma­tion of a non-prof­it 501c3 Foun­da­tion, called ‘BRAIN­net” (www.BRAINnet.net), through which sci­en­tists have access to many of these datasets for inde­pen­dent research.

Leave a Reply...

Loading Facebook Comments ...

Leave a Reply

Categories: Cognitive Neuroscience, Health & Wellness

Tags: , , , , , , , , , , , , , , , , , , , , , , ,

Watch All Recordings Now (40+ Speakers, 12+ Hours)

About SharpBrains

As seen in The New York Times, The Wall Street Journal, BBC News, CNN, Reuters and more, SharpBrains is an independent market research firm tracking health and performance applications of brain science.

Follow us and Engage via…

twitter_logo_header
RSS Feed

Search for anything brain-related in our article archives