William Langston

Last updated
J William Langston
Alma materUniversity of Missouri School of Medicine
Occupation(s)Neurologist; Founder, CEO, and Scientific Director of the Parkinson's Institute
Notable workThe Case of the Frozen Addicts

J. William Langston is the founder and chief scientific officer, movement disorder specialist, and chief executive officer of the Parkinson's Institute and Clinical Center in Sunnyvale, California, [1] the founding member of the Scientific Advisory Board for the Michael J. Fox Foundation [2] and the Co-Editor-in-Chief of the Journal of Parkinson's Disease. He is a graduate of the University of Missouri School of Medicine. Langston was formerly a faculty member at Stanford University and Chairman of Neurology at Santa Clara Valley Medical Center in San Jose, California. Langston has authored or co-authored some 360 peer-reviewed articles in the field of neurology, [3] most of which are on Parkinson's disease and related disorders. Langston gained national and international recognition in 1982 for the discovery of the link between a "synthetic heroin" contaminant (MPTP) and parkinsonism.

Contents

Career

In 1982 William Langston was head of neurology at Santa Clara Valley Medical Center when he made a major breakthrough in the research of Parkinson's Disease as a result of several incidents detailed in the book The Case of the Frozen Addicts. [4] Langston continued research into Parkinson's Disease and became an internationally known neuroscientist. He opened the Parkinson's Institute and Clinical Center in Sunnyvale, California in 1988 and became the chief executive officer and scientific director. Langston's current research interests include the study of mechanisms of neuronal degeneration, the etiology of Parkinson's disease, [5] and the development of new strategies to slow or halt disease progression such as cell replacement therapy and gene therapy and, more recently, the possible environmental causes of Parkinson's disease such as pesticides, [6] [7] cluster cases [8] [9] and the early identification of affected people through genome mapping. [10] In 2014 Carrolee Barlow became chief executive officer of the institute with Langston continuing as Chief Scientific Officer. [11]

During an interview in 2009 Langston stated: "I would never promise I could solve the disease. What I would do is say, I think there's a very real possibility, with the adequate funding, that we could make major progress on both finding the cause of the disease, which could lead to prevention, and also major progress on finding ways to slow and halt disease progression. I think that's a realistic possibility in my lifetime, my career. I wouldn't have said that five or 10 years ago. A cure, I will not say." [6]

The Case of the Frozen Addicts

The Case of the Frozen Addicts [4] was written by Langston and Jon Palfreman in 1995. A later edition was published in 2014. [12] The book details the work done by Langston, his colleagues and associates around the world to isolate the neurotoxic contaminant which caused the Parkinson's like symptoms in a number of heroin users and to develop methods of utilising this discovery. The book includes discovery of the dangers to researchers in handling the contaminant and some competition and contention between researchers.

William Langston was head of neurology at Santa Clara Valley Medical Center in 1982 when a drug offender was admitted who could neither move or talk. He had been admitted from the county jail and initially treated as a malingerer but later admitted to the psychiatric unit with suspected catatonic schizophrenia. During an examination of the patient, Langston noticed his fingers moving, perhaps voluntarily, and wrapped them around a pencil. The patient began to write notes that indicated that his mind was normal but his body was not responding. He had taken heroin before the symptoms developed. Through coincidental personal connections and media presentations another five patients with the same symptoms were discovered. All had what appeared to be symptoms of advanced Parkinson's Disease. In an attempt to save their lives Dr Langston administered L-dopa, a drug then recently introduced to treat Parkinson's Disease. The patients responded and could move and talk. (Unfortunately all six patients later developed severe side effects.) [13]

The common link between the patients was the batch of heroin they had taken. Medical and police research established that the batch of synthetic heroin all six patients had used contained a neurotoxic contaminant, MPTP. [14] MPTP (which sometimes taints MPPP, an effective synthetic opioid), is selectively toxic to the same nerve cells in the brain which die in Parkinson's disease, the substantia nigra. The discovery of the biologic effects of this compound led to a renaissance of the basic and clinical research in Parkinson's disease.

The clinical implications of this case were ground breaking. Parkinson's Disease is only experienced by humans but animal testing is essential in drug development. Now Parkinson's Disease symptoms could be induced in monkeys by using MPTP and research could begin into drugs to treat the disease. "[W]hat had started as a drug tragedy was to open a new chapter of medical research which would offer hope to Parkinson's disease sufferers throughout the world." [4] : 29 

Awards

Langston has received numerous awards, including the Distinguished Achievement Award from Modern Medicine, the Sarah M. Poiley Award from the New York Academy of Sciences, the 30th Anniversary Award from the Parkinson's Disease Foundation in 1987, [15] the Distinguished Clinical Investigator Award from Roche Pharmaceuticals, the 1999 Movement Disorders Research Award [16] from the American Academy of Neurology, the 2008 Donald Calne Lectureship [17] and 2012 Robert A. Pritzker Prize for Leadership in Parkinson's Research [18] from The Michael J. Fox Foundation for Parkinson's Research.

Selected publications

Related Research Articles

<span class="mw-page-title-main">Substantia nigra</span> Structure in the basal ganglia of the brain

The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. Substantia nigra is Latin for "black substance", reflecting the fact that parts of the substantia nigra appear darker than neighboring areas due to high levels of neuromelanin in dopaminergic neurons. Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta.

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

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is an organic compound. It is classified as a tetrahydropyridine. It is of interest as a precursor to the neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study disease models in various animals.

<span class="mw-page-title-main">Desmethylprodine</span> Opioid analgesic drug

Desmethylprodine or 1-methyl-4-phenyl-4-propionoxypiperidine is an opioid analgesic drug developed in the 1940s by researchers at Hoffmann-La Roche. Desmethylprodine has been labeled by the DEA as a Schedule I drug in the United States. It is an analog of pethidine (meperidine) a Schedule II drug. Chemically, it is a reversed ester of pethidine which has about 70% of the potency of morphine. Unlike its derivative prodine, it was not reported to exhibit optical isomerism. It was reported to have 30 times the activity of pethidine and a greater analgesic effect than morphine in rats, and it was demonstrated to cause central nervous system stimulation in mice.

Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifically, a neurotoxin or neurotoxicant– alters the normal activity of the nervous system in such a way as to cause permanent or reversible damage to nervous tissue. This can eventually disrupt or even kill neurons, which are cells that transmit and process signals in the brain and other parts of the nervous system. Neurotoxicity can result from organ transplants, radiation treatment, certain drug therapies, recreational drug use, exposure to heavy metals, bites from certain species of venomous snakes, pesticides, certain industrial cleaning solvents, fuels and certain naturally occurring substances. Symptoms may appear immediately after exposure or be delayed. They may include limb weakness or numbness, loss of memory, vision, and/or intellect, uncontrollable obsessive and/or compulsive behaviors, delusions, headache, cognitive and behavioral problems and sexual dysfunction. Chronic mold exposure in homes can lead to neurotoxicity which may not appear for months to years of exposure. All symptoms listed above are consistent with mold mycotoxin accumulation.

<span class="mw-page-title-main">Natural resistance-associated macrophage protein 2</span>

Natural resistance-associated macrophage protein 2, also known as divalent metal transporter 1 (DMT1) and divalent cation transporter 1 (DCT1), is a protein that in humans is encoded by the SLC11A2 gene. DMT1 represents a large family of orthologous metal ion transporter proteins that are highly conserved from bacteria to humans.

<span class="mw-page-title-main">PEPAP</span> Opioid analgesic drug

PEPAP (phenethylphenylacetoxypiperidine) is an opioid analgesic that is an analog of desmethylprodine.

MPP<sup>+</sup> Chemical compound

MPP+ (1-methyl-4-phenylpyridinium) is a positively charged organic molecule with the chemical formula C12H12N+. It is a neurotoxin that acts by interfering with oxidative phosphorylation in mitochondria by inhibiting complex I, leading to the depletion of ATP and eventual cell death.

<span class="mw-page-title-main">LY-503430</span> Chemical compound

LY-503430 is an AMPA receptor positive allosteric modulator developed by Eli Lilly.

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

Piroheptine is an anticholinergic and antihistamine used as an antiparkinsonian agent.

<span class="mw-page-title-main">4-Benzylpiperidine</span> Chemical compound

4-Benzylpiperidine is a drug and research chemical used in scientific studies. It acts as a monoamine releasing agent with 20- to 48-fold selectivity for releasing dopamine versus serotonin. It is most efficacious as a releaser of norepinephrine, with an EC50 of 109 nM (DA), 41.4 nM (NE) and 5246 nM (5-HT). It has a fast onset of action and a short duration. It also functions as a monoamine oxidase inhibitor (MAOI) with preference for MAO-A.

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

Befiradol is an experimental drug being studied for the treatment of levodopa-induced dyskinesia. It is a potent and selective 5-HT1A receptor full agonist.

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

Traxoprodil is a drug developed by Pfizer which acts as an NMDA antagonist, selective for the NR2B subunit. It has neuroprotective, analgesic, and anti-Parkinsonian effects in animal studies. Traxoprodil has been researched in humans as a potential treatment to lessen the damage to the brain after stroke, but results from clinical trials showed only modest benefit. The drug was found to cause EKG abnormalities and its clinical development was stopped. More recent animal studies have suggested traxoprodil may exhibit rapid-acting antidepressant effects similar to those of ketamine, although there is some evidence for similar psychoactive side effects and abuse potential at higher doses, which might limit clinical acceptance of traxoprodil for this application.

<span class="mw-page-title-main">SIB-1553A</span> Chemical compound

SIB-1553A is a nicotinic acetylcholine receptor agonist that is selective for receptors with a β4 subunit. Administration of SIB-1553A improved memory and attention in a Parkinson's disease model.

<span class="mw-page-title-main">UWA-101</span> Chemical compound

UWA-101 is a phenethylamine derivative invented by Dr Matthew Piggott at the University of Western Australia, and researched as a potential treatment for Parkinson's disease. Its chemical structure is very similar to that of the illegal drug MDMA, the only difference being the replacement of the α-methyl group with an α-cyclopropyl group. MDMA has been found in animal studies and reported in unauthorised human self-experiments to be effective in the short-term relief of side-effects of Parkinson's disease therapy, most notably levodopa-induced dyskinesia. However the illegal status of MDMA and concerns about its potential for recreational use, neurotoxicity and potentially dangerous side effects mean that it is unlikely to be investigated for medical use in this application, and so alternative analogues were investigated.

Irwin J. "Irv" Kopin (1929–2017) was an American biochemist, best known for his research on the function and metabolism of catecholamines.

Parthanatos is a form of programmed cell death that is distinct from other cell death processes such as necrosis and apoptosis. While necrosis is caused by acute cell injury resulting in traumatic cell death and apoptosis is a highly controlled process signalled by apoptotic intracellular signals, parthanatos is caused by the accumulation of Poly(ADP ribose) (PAR) and the nuclear translocation of apoptosis-inducing factor (AIF) from mitochondria. Parthanatos is also known as PARP-1 dependent cell death. PARP-1 mediates parthanatos when it is over-activated in response to extreme genomic stress and synthesizes PAR which causes nuclear translocation of AIF. Parthanatos is involved in diseases that afflict hundreds of millions of people worldwide. Well known diseases involving parthanatos include Parkinson's disease, stroke, heart attack, and diabetes. It also has potential use as a treatment for ameliorating disease and various medical conditions such as diabetes and obesity.

In ophthalmology, apraxia of lid opening (ALO) is an inability to initiate voluntary opening of the eyelid following a period of eyelid closure, with normal function at other times. Manual lifting of the eyelid often resolves the problem and the lid is able to stay open.

Ted M. Dawson is an American neurologist and neuroscientist. He is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and Director of the Institute for Cell Engineering at Johns Hopkins University School of Medicine. He has joint appointments in the Department of Neurology, Neuroscience and Department of Pharmacology and Molecular Sciences.

Yaakov Stern is an American cognitive neuroscientist, professor of neuropsychology at Columbia University.

<span class="mw-page-title-main">Animal models of Parkinson's disease</span> Models used in Parkinsons disease research

Animal models of Parkinson's disease are essential in the research field and widely used to study Parkinson's disease. Parkinson's disease is a neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The loss of the dopamine neurons in the brain, results in motor dysfunction, ultimately causing the four cardinal symptoms of PD: tremor, rigidity, postural instability, and bradykinesia. It is the second most prevalent neurodegenerative disease, following Alzheimer's disease. It is estimated that nearly one million people could be living with PD in the United States.

References

  1. ↑ "Staff Directory". www.thepi.org. Retrieved 2016-03-09.
  2. ↑ "The Michael J. Fox Foundation for Parkinson's Research". The Michael J. Fox Foundation. Retrieved 2016-03-09.
  3. ↑ "Profile: J. William Langston | Journal of Parkinson's Disease". www.journalofparkinsonsdisease.com. Retrieved 2016-03-09.
  4. 1 2 3 Langston, J William; Palfreman, Jon (1995). The Case of the Frozen Addicts. New York: Pantheon Books. ISBN   0-679-42465-2.
  5. ↑ Langston, J. William (1996-12-01). "The etiology of Parkinson's disease with emphasis on the MPTP story". Neurology. 47 (6 Suppl 3): 153S–160S. doi:10.1212/WNL.47.6_Suppl_3.153S. ISSN   0028-3878. PMID   8959984. S2CID   41353714.
  6. 1 2 "FRONTLINE: my father, my brother, and me: interviews: dr. william langston PBS". www.pbs.org. Retrieved 2016-03-28.
  7. ↑ Wallis, Claudia (2001-06-24). "Surprising Clue to Parkinson's". Time. Retrieved 2016-03-28.
  8. ↑ Duenwald, Mary (2002-05-14). "Parkinson's 'Clusters' Getting a Closer Look". The New York Times. ISSN   0362-4331 . Retrieved 2016-03-28.
  9. ↑ Hawaleshka, D. (2002-06-24). "Clusters of parkinson's". Maclean's: 115, 50. ProQuest   218538896.
  10. ↑ Yoffe, Emily (2010-08-24). "The Medical Revolution". Slate. ISSN   1091-2339 . Retrieved 2016-03-28.
  11. ↑ "Carrolee Barlow, MD, PhD to Lead the Parkinson\'s Institute and Clinical Center as Chief Executive Officer | Evaluate". www.evaluategroup.com. Retrieved 2016-04-10.
  12. ↑ Langston, J William; Palfreman, Jon (2014). The Case of the Frozen Addicts (2nd ed.). New York: Pantheon Books. ISBN   978-1-61499-331-5.
  13. ↑ Palfreman, Jon (2015). Brain Storms: The race to unlock the mysteries of Parkinson's. London: Penguin Random House UK. pp. 3–5. ISBN   9781846044946.
  14. ↑ Palfreman, p. 44.
  15. ↑ "Parkinson's Disease Foundation 50th Anniversary Educational Symposium Program" (PDF). 11 October 2007. p. 8. Retrieved 9 March 2016.
  16. ↑ "Awards History | American Academy of Neurology®". www.aan.com. Retrieved 2016-03-09.
  17. ↑ "Donald Calne Lectureship Parkinson Canada". www.parkinson.ca. Retrieved 2016-03-28.
  18. ↑ "J. William Langston, MD, Awarded 2012 Robert A. Pritzker Prize for Leadership in Parkinson's Research by The Michael J. Fox Foundation | Parkinson's Disease Information". The Michael J. Fox Foundation. Retrieved 2016-03-09.
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