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Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. dliu@hhmi.org

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The research enterprise is confusing to most people, even for advanced students... How do results get transferred to medical advances? Toto talks about his research in his 2009 HHMI Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html) and has developed a website aimed at providing teachers and students with information about cone snails (www.theconesnail.com)... Currently a number of other peptide toxins derived from cone snails are in development to treat Parkinson's disease, epilepsy, heart disease, and pain... The animation found at www.hhmi.org/biointeractive/biodiversity/2009_prialt_blocks_motor.html shows the physiological action of ω-conotoxin... By the 1950s and 1960s, research had associated atherosclerosis with heart disease and established that artery-clogging plaques were composed largely of cholesterol... It was also known that HMG-CoA reductase was the rate-limiting enzyme on the path to making cholesterol... By the early 1970s, drug company employee Akira Endo was screening bacterial and fungal cultures to find inhibitors of HMG-CoA reductase... He soon found a candidate, the first member of the class now known as statins... They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem. ” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html)... Brown and Goldstein discovered the answer to the delivery problem: Cells had receptors on their surface that bound cholesterol-rich LDL particles... Once separated from the LDL, the receptor could be recycled to the cell surface... The simple animation found on the W.H... Freeman website (http://bcs.whfreeman.com/thelifewire/content/chp05/0502003.html) illustrates endocytosis and recycling of LDL receptors, but not feedback regulation... Lowering the cholesterol content in liver cells could up-regulate LDL receptors, providing more receptors for taking LDL out of the bloodstream, thus lowering serum cholesterol levels and inhibiting plaque formation.

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Patients affected by FH develop hard cholesterol-filled nodules and have heart attacks as early as age 5. From the Brown and Goldstein lab pages.
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Figure 6: Patients affected by FH develop hard cholesterol-filled nodules and have heart attacks as early as age 5. From the Brown and Goldstein lab pages.

Mentions: In the late 1960s, physicians Michael Brown and Joseph Goldstein saw their first patients suffering from a severe form of inherited hypercholesterolemia called familial hypercholesterolemia (FH). These individuals can have serum cholesterol levels 10 times that of an average person, and they develop thick deposits of cholesterol called xanthomas that can be seen on various parts of the body (Figure 6). Brown and Goldstein's approach was to use this genetic disease as a way to understand the more general phenomena of high cholesterol affecting the general population. They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem.” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html). Their lab website presents a good short history of this work as well (www4.utsouthwestern.edu/moleculargenetics/pages/gold/past.html). Although I think Brown and Goldstein would probably call themselves disease-oriented researchers, it's significant that they sought training in basic research and have followed a basic research approach to understanding disease. As a result, their work established important concepts in cell biology, a case of medically oriented research contributing to basic research advances. Their cholesterol work has elucidated receptor-mediated endocytosis, recycling of membrane receptors, and feedback regulation of receptors. These principles are outlined in a review article on their website (www4.utsouthwestern.edu/moleculargenetics/pdf/msb_cur_res/2009%20ATVB%20Brown%20431.pdf).Figure 6.


Where do new medicines come from?

Liu D - CBE Life Sci Educ (2011)

Patients affected by FH develop hard cholesterol-filled nodules and have heart attacks as early as age 5. From the Brown and Goldstein lab pages.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3105917&req=5

Figure 6: Patients affected by FH develop hard cholesterol-filled nodules and have heart attacks as early as age 5. From the Brown and Goldstein lab pages.
Mentions: In the late 1960s, physicians Michael Brown and Joseph Goldstein saw their first patients suffering from a severe form of inherited hypercholesterolemia called familial hypercholesterolemia (FH). These individuals can have serum cholesterol levels 10 times that of an average person, and they develop thick deposits of cholesterol called xanthomas that can be seen on various parts of the body (Figure 6). Brown and Goldstein's approach was to use this genetic disease as a way to understand the more general phenomena of high cholesterol affecting the general population. They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem.” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html). Their lab website presents a good short history of this work as well (www4.utsouthwestern.edu/moleculargenetics/pages/gold/past.html). Although I think Brown and Goldstein would probably call themselves disease-oriented researchers, it's significant that they sought training in basic research and have followed a basic research approach to understanding disease. As a result, their work established important concepts in cell biology, a case of medically oriented research contributing to basic research advances. Their cholesterol work has elucidated receptor-mediated endocytosis, recycling of membrane receptors, and feedback regulation of receptors. These principles are outlined in a review article on their website (www4.utsouthwestern.edu/moleculargenetics/pdf/msb_cur_res/2009%20ATVB%20Brown%20431.pdf).Figure 6.

View Article: PubMed Central - PubMed

Affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. dliu@hhmi.org

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

The research enterprise is confusing to most people, even for advanced students... How do results get transferred to medical advances? Toto talks about his research in his 2009 HHMI Holiday Lectures (www.hhmi.org/biointeractive/biodiversity/lectures.html) and has developed a website aimed at providing teachers and students with information about cone snails (www.theconesnail.com)... Currently a number of other peptide toxins derived from cone snails are in development to treat Parkinson's disease, epilepsy, heart disease, and pain... The animation found at www.hhmi.org/biointeractive/biodiversity/2009_prialt_blocks_motor.html shows the physiological action of ω-conotoxin... By the 1950s and 1960s, research had associated atherosclerosis with heart disease and established that artery-clogging plaques were composed largely of cholesterol... It was also known that HMG-CoA reductase was the rate-limiting enzyme on the path to making cholesterol... By the early 1970s, drug company employee Akira Endo was screening bacterial and fungal cultures to find inhibitors of HMG-CoA reductase... He soon found a candidate, the first member of the class now known as statins... They were also interested in the basic research problem of how insoluble cholesterol could be delivered to cells—“the delivery problem. ” I recommend visiting their Nobel Prize webpages and in particular reading the transcript of their Nobel lecture (http://nobelprize.org/nobel_prizes/medicine/laureates/1985/goldstein-lecture.html)... Brown and Goldstein discovered the answer to the delivery problem: Cells had receptors on their surface that bound cholesterol-rich LDL particles... Once separated from the LDL, the receptor could be recycled to the cell surface... The simple animation found on the W.H... Freeman website (http://bcs.whfreeman.com/thelifewire/content/chp05/0502003.html) illustrates endocytosis and recycling of LDL receptors, but not feedback regulation... Lowering the cholesterol content in liver cells could up-regulate LDL receptors, providing more receptors for taking LDL out of the bloodstream, thus lowering serum cholesterol levels and inhibiting plaque formation.

Show MeSH
Related in: MedlinePlus