Jonathan Sackner-Bernstein

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Jonathan Sackner-Bernstein
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Sackner-Bernstein in 2019
Born1961 (age 6162)
NationalityAmerican
Alma mater Miami Beach Senior High School
University of Pennsylvania
Moore School of Electrical Engineering
Jefferson Medical College
OccupationCardiologist
Organization(s) Mt. Sinai Hospital
Columbia University
Food and Drug Administration
DARPA
ExVivos
Known forBiotech, Medtech, Clinical Research
SpouseAudrey S. Bernstein

Jonathan Sackner-Bernstein is an American physician. He has published around 80 scientific articles, which have been cited more than 4,000 times. [1] His research has ranged from cardiac care to the efficacy of drugs. His research led to increased scrutiny of Nesiritide, a widely marketed drug, which led to its decline in its use. [2]

Contents

Education

Sackner-Bernstein graduated from the University of Pennsylvania's Moore School of Electrical Engineering in 1983 (BSEE),. He completed his MD from Jefferson Medical College, during which he moonlit writing code. [3] He completed a residency in internal medicine and subsequently cardiology at Mount Sinai Hospital in New York. In addition, Sackner-Bernstein completed a research fellowship in heart failure under Milton Packer at Mount Sinai. [4]

Academic, clinical and research experience

Sackner-Bernstein joined the Columbia University faculty in 1993 in the Division of Circulatory Physiology, where he established its clinical research program. He accumulated a large experience with the beta-blocker carvedilol prior to the application by its developer (GlaxoSmithKline) to the US Food and Drug Administration (FDA). [5]

His most cited research focused on whether the newly marketed heart failure drug nesiritide (hr-BNP, Natrecor) was safe and effective, with a call for large-scale clinical trials prior to widespread use. [6] [7] [8] While nesiritide was projected to generate $1 billion in sales in 2006, [9] these studies triggered controversy [10] [11] that eventually led to markedly lower use by physicians. [12]

Other frequently cited articles include work on Carvedilol [13] and cardiac hypertrophy. [14]

He is also the author of a book on heart disease, Before It Happens To You. [15]

US government projects

Sackner-Bernstein joined the FDA in 2008 as Associate Center Director, leading Post Market Operations as well as Technology and Innovation programs. [16] As the Center's first Associate Center Director for Technology and Innovation, Sackner-Bernstein launched the Innovation Initiative in 2011, [17] which subsequently led to the Early Feasibility Program and laid the foundation for the Breakthrough Device Program.

He also helped establish a formal relationship between FDA and DARPA (Defense Advanced Research Projects Agency), [18] then serving as architect for the initial Entrepreneurs-in-Residence Program. sponsored by the White House Office of Science and Technology Policy (OSTP) [19]

Commercial projects

Sackner-Bernstein conducted the first study to estimate the amount of dopamine free in the cytosol of the dopaminergic neurons in people with Parkinson's. [20] While confirming that tissue levels of dopamine are markedly reduced, statistical adjustments for the loss of neurons, axons and intracellular vesicles demonstrated that free dopamine levels trended higher in the caudate and were significantly elevated in the putamen. In parallel, multiple preclinical studies showed that use of a drug to reduce dopamine improved biology and function. [21] [22] [23] The data suggest that the neurons that drive Parkinson's experience the disease as a state of dopamine excess - not deficiency, relevant because of potential for dopamine's break-down products causing neuronal toxicity. Sackner-Bernstein launched a company to test such a drug treatment strategy in Parkinson's. [24]



Related Research Articles

<span class="mw-page-title-main">Beta blocker</span> Class of medications used to manage abnormal heart rhythms

Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms (arrhythmia), and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients.

<span class="mw-page-title-main">Bromocriptine</span> Organic Chemical Compound

Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes.

An inotrope or inotropic is a drug or any substance that alters the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions. Positively inotropic agents increase the strength of muscular contraction.

<small>L</small>-DOPA Chemical compound

l-DOPA, also known as levodopa and l-3,4-dihydroxyphenylalanine, is an amino acid that is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize l-DOPA, make it via biosynthesis from the amino acid l-tyrosine. l-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), which are collectively known as catecholamines. Furthermore, l-DOPA itself mediates neurotrophic factor release by the brain and CNS. l-DOPA can be manufactured and in its pure form is sold as a psychoactive drug with the INN levodopa; trade names include Sinemet, Pharmacopa, Atamet, and Stalevo. As a drug, it is used in the clinical treatment of Parkinson's disease and dopamine-responsive dystonia.

<span class="mw-page-title-main">Nadolol</span> Non-selective beta blocker used in the treatment of high blood pressure and chest pain

Nadolol, sold under the brand name Corgard among others, is a medication used to treat high blood pressure, heart pain, atrial fibrillation, and some inherited arrhythmic syndromes. It has also been used to prevent migraine headaches and complications of cirrhosis. It is taken orally.

<span class="mw-page-title-main">Cabergoline</span> Chemical compound

Cabergoline, sold under the brand name Dostinex among others, is a dopaminergic medication used in the treatment of high prolactin levels, prolactinomas, Parkinson's disease, and for other indications. It is taken by mouth.

<span class="mw-page-title-main">Reserpine</span> Drug used to treat high blood pressure

Reserpine is a drug that is used for the treatment of high blood pressure, usually in combination with a thiazide diuretic or vasodilator. Large clinical trials have shown that combined treatment with reserpine plus a thiazide diuretic reduces mortality of people with hypertension. Although the use of reserpine as a solo drug has declined since it was first approved by the FDA in 1955, the combined use of reserpine and a thiazide diuretic or vasodilator is still recommended in patients who do not achieve adequate lowering of blood pressure with first-line drug treatment alone. The reserpine-hydrochlorothiazide combo pill was the 17th most commonly prescribed of the 43 combination antihypertensive pills available In 2012.

<span class="mw-page-title-main">Hypertensive heart disease</span> Medical condition

Hypertensive heart disease includes a number of complications of high blood pressure that affect the heart. While there are several definitions of hypertensive heart disease in the medical literature, the term is most widely used in the context of the International Classification of Diseases (ICD) coding categories. The definition includes heart failure and other cardiac complications of hypertension when a causal relationship between the heart disease and hypertension is stated or implied on the death certificate. In 2013 hypertensive heart disease resulted in 1.07 million deaths as compared with 630,000 deaths in 1990.

<span class="mw-page-title-main">Nesiritide</span>

Nesiritide, sold under the brand name Natrecor, is the recombinant form of the 32 amino acid human B-type natriuretic peptide, which is normally produced by the ventricular myocardium. Nesiritide works to facilitate cardiovascular fluid homeostasis through counterregulation of the renin–angiotensin–aldosterone system, stimulating cyclic guanosine monophosphate, leading to smooth muscle cell relaxation.

<span class="mw-page-title-main">Bisoprolol</span> Beta-1 selective adrenenergic blocker medication used to treat cardiovascular diseases

Bisoprolol, sold under the brand name Zebeta among others, is a beta blocker medication used for heart diseases. This includes tachyarrhythmias, high blood pressure, chest pain from not enough blood flow to the heart, and heart failure. It is taken by mouth.

<span class="mw-page-title-main">Carvedilol</span> Oral blood-pressure medication

Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure (CHF), and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is generally a second-line treatment. It is taken by mouth.

<span class="mw-page-title-main">Trihexyphenidyl</span> Antispasmodic & used in treatment for Parkinsons disease

Trihexyphenidyl is an antispasmodic drug used to treat stiffness, tremors, spasms, and poor muscle control. It is an agent of the antimuscarinic class and is often used in management of Parkinson's disease. It was approved by the FDA for the treatment of Parkinson's in the US in 2003.

<span class="mw-page-title-main">Dopamine agonist</span> Compound that activates dopamine receptors

A dopamine agonist(DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used in the treatment of Parkinson's disease, and to a lesser extent, in hyperprolactinemia and restless legs syndrome. They are also used off-label in the treatment of clinical depression. The use of dopamine agonists is associated with impulse control disorders and dopamine agonist withdrawal syndrome (DAWS).

<span class="mw-page-title-main">Levosimendan</span> Pharmaceutical drug

Levosimendan (INN) is a calcium sensitizer used in the management of acutely decompensated congestive heart failure. It is marketed under the trade name Simdax. Overall the drug has a two fold mechanism of action. It leads to greater inotrophy by increasing the calcium sensitivity as it binds to troponin and this results in a greater positive inotrophic force. Secondly, the drug is able to open ATP sensitive potassium channels in vascular smooth muscle cells, and the vascular dilatory effects of the drug lead to a decreased preload and afterload, putting less work on the heart. This drug is in the process of review by the FDA but has not been approved for use in the United States yet.

<span class="mw-page-title-main">Nebivolol</span> Chemical compound

Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. It is taken by mouth.

<span class="mw-page-title-main">Rasagiline</span> Chemical compound

Rasagiline is an irreversible inhibitor of monoamine oxidase-B used as a monotherapy to treat symptoms in early Parkinson's disease or as an adjunct therapy in more advanced cases.

<span class="mw-page-title-main">Dronedarone</span> Drug

Dronedarone, sold under the brand name Multaq, is a medication by Sanofi-Aventis, mainly for the indication of cardiac arrhythmias. It was approved by the FDA on July 2, 2009. It was recommended as an alternative to amiodarone for the treatment of atrial fibrillation and atrial flutter in people whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment i.e. direct current cardioversion (DCCV) to maintain normal rhythm. It is a class III antiarrhythmic drug. In the United States, the FDA approved label includes a claim for reducing hospitalization, but not for reducing mortality, as a reduction in mortality was not demonstrated in the clinical development program. A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in patients with moderate to severe CHF.

<span class="mw-page-title-main">Alpha blocker</span> Class of pharmacological agents

Alpha-blockers, also known as α-blockers or α-adrenoreceptor antagonists, are a class of pharmacological agents that act as antagonists on α-adrenergic receptors (α-adrenoceptors).

<span class="mw-page-title-main">Acute decompensated heart failure</span> Medical condition

Acute decompensated heart failure (ADHF) is a sudden worsening of the signs and symptoms of heart failure, which typically includes difficulty breathing (dyspnea), leg or feet swelling, and fatigue. ADHF is a common and potentially serious cause of acute respiratory distress. The condition is caused by severe congestion of multiple organs by fluid that is inadequately circulated by the failing heart. An attack of decompensation can be caused by underlying medical illness, such as myocardial infarction, an abnormal heart rhythm, infection, or thyroid disease.

<span class="mw-page-title-main">Brain natriuretic peptide 32</span> Hormone secreted in the heart

Brain natriuretic peptide 32 (BNP), also known as B-type natriuretic peptide, is a hormone secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. Along with NT-proBNP, BNP is one of two natriuretic peptides.

References

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  2. Saul, Stephanie (2005-05-17). "The Marketing and Success of Natrecor". The New York Times.
  3. Creative Computing Magazine (December 1983) Volume 09 Number 12. December 1983.
  4. "Medscape: Medscape Access".
  5. European Heart Journal (abstract P1651): http://eurheartj.oxfordjournals.org/content/ehj/21/Abstract_Supplement/1.full.pdf
  6. Sackner-Bernstein, JD; Skopicki, HA; Aaronson, KD (Mar 2005). "Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure". Circulation. 111 (12): 1487–91. doi: 10.1161/01.CIR.0000159340.93220.E4 . PMID   15781736.
  7. Sackner-Bernstein, JD; Kowalski, M; Fox, M; Aaronson, K (2005). "Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials". JAMA. 293 (15): 1900–5. doi:10.1001/jama.293.15.1900. PMID   15840865.
  8. Aaronson, KD; Sackner-Bernstein, J (2006). "Risk of death associated with nesiritide in patients with acutely decompensated heart failure". JAMA. 296 (12): 1465–6. doi:10.1001/jama.296.12.1465. PMID   17003394.
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  15. "Nonfiction Book Review: Before It Happens to You: A Breakthrough Program for Reversing or Preventing Heart Disease by Jonathan Sackner-Bernstein". PublishersWeekly.com. February 2004.
  16. "Sackner-Bernstein moves to the FDA". Medscape. Retrieved 2023-04-04.
  17. "Perspective: CDRH's Innovation Pathway: Will It Get Your Device to Market Faster?". www.raps.org. Retrieved March 3, 2023.
  18. Dec 2010: https://www.gpo.gov/fdsys/pkg/FR-2010-12-20/html/2010-31811.htm
  19. https://www.signup4.net/Upload/BOOZ12A/CTSA37E/File%208_Speaker%20Biographies.pdf [ bare URL PDF ]
  20. Sackner-Bernstein, J (2021). "Estimates of Intracellular Dopamine in Parkinson's Disease: A Systematic Review and Meta-Analysis". Journal of Parkinson's Disease. 11 (3): 1011–1018. doi:10.3233/JPD-212715. PMC   8461729 . PMID   34024786.
  21. Choi, SJ; Panhelainen, A; Schmitz, Y; Larsen, KE; Kanter, E; Wu, M; Sulzer, D; Mosharov, EV (Mar 2015). "Changes in neuronal dopamine homeostasis following 1-methyl-4-phenylpyridinium (MPP+) exposure". Journal of Biological Chemistry. 290 (11): 6799–6809. doi: 10.1074/jbc.M114.631556 . PMC   4358106 . PMID   25596531.
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  23. Zhou, ZD; Saw, WT; Ho, PGH; Zhang, ZW; Zeng, L; Chang, YY; Sun, AXY; Ma, DR; Wang, HY; Zhou, L; Lim, KL; Tan, E-K (Nov 2022). "The role of tyrosine hydroxylase-dopamine pathway in Parkinson's disease pathogenesis". Cellular and Molecular Life Sciences. 79 (12): 599. doi:10.1007/s00018-022-04574-x. PMC   9678997 . PMID   36409355.
  24. "Exploring Breakthroughs in Parkinson's Disease Treatment". Techonomy: A Worth Media Group Brand. Retrieved 2023-11-03.