Lee Sweeney

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H. Lee Sweeney is an American scientist who studies muscle.

Contents

Education and career

He received his undergraduate degree in biochemistry from Massachusetts Institute of Technology in 1975 and his PhD from Harvard in physiology and biophysics in 1984. [1] He then spent a year as research instructor in physiology at the University of Texas Southwestern Medical School, and then obtained an appointment as an assistant professor at the University of Texas at Austin. [2]

He joined the faculty of the University of Pennsylvania in 1989, became chair of the department of physiology in 1999, became founding director of the Paul D. Wellstone Muscular Dystrophy Cooperative Research Center in 2005. and eventually obtained an endowed chair and became director of the Penn Center for Orphan Disease Research and Therapy, which was founded in 2012. [2] [3]

He left Penn and joined the faculty of University of Florida College of Medicine in 2015, where he became the Thomas H. Maren M.D. Eminent Scholar Chair in Pharmacology and Therapeutics and became the director of the new Myology Institute there. [3]

Research

In 1998 his lab published work in which they used gene therapy to incorporate an extra copy of IGF1 into muscle cells of young and old mice; age-related muscle aging in the older mice was reversed and both old and mice became stronger. The paper received national press coverage, and the mice became known as "Schwarzenegger mice." He soon started receiving calls from athletes and coaches asking him to use this method for gene doping; he was still receiving inquires as of 2008. [4] [5] He has written on the topic of gene doping in popular media [6] and is often called upon to comment on the topic in the media. [7] [8] [9]

Sweeney collaborated with PTC Therapeutics in the discovery and development of ataluren. [10] [11] which was initially funded in part by Parent Project Muscular Dystrophy. [12] Sweeney's lab had published work in 1999 showing that gentamicin could "cure" a rodent model of Duchenne muscular dystrophy [10] [13] and this led to the collaboration with PTC that produced ataluren—Sweeney was the last author on the initial publication of ataluren in Nature in 2007. [14] Ataluren was approved to treat DMD in Europe in 2014. [15]

As of 2012 he had been an author on around 180 papers and reviews that had been cited around 16,000 times. [2]

Along with serving on the scientific advisory board of PTC, he does likewise with Cytokinetics [16] and Solid Biosciences [17] He is also on the scientific advisory board of the Parent Project Muscular Dystrophy. [18]

Related Research Articles

<span class="mw-page-title-main">Muscular dystrophy</span> Genetic disorder

Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Some types are also associated with problems in other organs.

In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in leading to a truncated, incomplete, and nonfunctional protein product. Nonsense mutation is not always harmful, the functional effect of a nonsense mutation depends on many aspects, such as the location of the stop codon within the coding DNA. For example, the effect of a nonsense mutation depends on the proximity of the nonsense mutation to the original stop codon, and the degree to which functional subdomains of the protein are affected. As nonsense mutations leads to premature termination of polypeptide chains; they are also called chain termination mutations.

<span class="mw-page-title-main">Myostatin</span> Mammalian and avian protein

Myostatin is a protein that in humans is encoded by the MSTN gene. Myostatin is a myokine that is produced and released by myocytes and acts on muscle cells to inhibit muscle growth. Myostatin is a secreted growth differentiation factor that is a member of the TGF beta protein family.

<span class="mw-page-title-main">Dystrophin</span> Rod-shaped cytoplasmic protein

Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex (DAPC). Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere. It has a molecular weight of 427 kDa

<span class="mw-page-title-main">Duchenne muscular dystrophy</span> Type of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis followed by the arms. This can result in trouble standing up. Most are unable to walk by the age of 12. Affected muscles may look larger due to increased fat content. Scoliosis is also common. Some may have intellectual disability. Females with a single copy of the defective gene may show mild symptoms.

<span class="mw-page-title-main">Becker muscular dystrophy</span> Genetic muscle disorder

Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis. It is a type of dystrophinopathy. This is caused by mutations in the dystrophin gene, which encodes the protein dystrophin. Becker muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene, but has a milder course.

Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre-mRNA, direct steric blockage, and exon content modulation through splicing site binding on pre-mRNA. Several ASOs have been approved in the United States, the European Union, and elsewhere.

Sarepta Therapeutics, Inc. is a medical research and drug development company with corporate offices and research facilities in Cambridge, Massachusetts, United States. Incorporated in 1980 as AntiVirals, shortly before going public the company changed its name from AntiVirals to AVI BioPharma soon with stock symbol AVII and in July 2012 changed name from AVI BioPharma to Sarepta Therapeutics and SRPT respectively. As of the end of 2019, the company has two approved drugs.

The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. It is one of the two protein complexes that make up the costamere in striated muscle cells. The other complex is the integrin-vinculin-talin complex.

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

Deflazacort is a glucocorticoid used as an anti-inflammatory and immunomodulatory agent. It was patented in 1965 and approved for medical use in 1985. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication for Duchenne Muscular Dystrophy.

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

Ataluren, sold under the brand name Translarna, is a medication for the treatment of Duchenne muscular dystrophy. It was designed by PTC Therapeutics.

Biostrophin is a drug which may serve as a vehicle for gene therapy, in the treatment of Duchenne and Becker muscular dystrophy.

<span class="mw-page-title-main">Eric N. Olson</span> American molecular biologist

Eric Newell Olson is an American molecular biologist. He is professor and chair of the Department of Molecular Biology at the University of Texas Southwestern Medical Center in Dallas, where he also holds the Robert A. Welch Distinguished Chair in Science, the Annie and Willie Nelson Professorship in Stem Cell Research, and the Pogue Distinguished Chair in Research on Cardiac Birth Defects.

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

Ezutromid is an orally administered small molecule utrophin modulator involved in a Phase 2 clinical trial produced by Summit Therapeutics for the treatment of Duchenne muscular dystrophy (DMD). DMD is a fatal x-linked recessive disease affecting approximately 1 in 5000 males and is a designated orphan disease by the FDA and European Medicines Agency. Approximately 1/3 of the children obtain DMD as a result of spontaneous mutation in the dystrophin gene and have no family history of the disease. Dystrophin is a vital component of mature muscle function, and therefore DMD patients have multifarious forms of defunct or deficient dystrophin proteins that all manifest symptomatically as muscle necrosis and eventually organ failure. Ezutromid is theorized to maintain utrophin, a protein functionally and structurally similar to dystrophin that precedes and is replaced by dystrophin during development. Utrophin and dystrophin are reciprocally expressed, and are found in different locations in a mature muscle cell. However, in dystrophin-deficient patients, utrophin was found to be upregulated and is theorized to replace dystrophin in order to maintain muscle fibers. Ezutromid is projected to have the potential to treat all patients suffering with DMD as it maintains the production of utrophin to counteract the lack of dystrophin to retard muscle degeneration. Both the FDA and European Medicines Agency has given ezutromid an orphan drug designation. The FDA Office of Orphan Products and Development offers an Orphan Drug Designation program (ODD) that allows drugs aimed to treat diseases that affect less than 200,000 people in the U.S. monetary incentives such as a period of market exclusivity, tax incentives, and expedited approval processes.

Michel Fardeau, born on 24 October 1929 in Paris 12th arrondissement, is a medical researcher in medical pathology, pioneering founder in France of myology, a medical discipline treating diseases of the neuromuscular system. He was also a full professor at the Conservatoire National des Arts et Métiers in a chair dedicated to the social integration of disabled people.

<span class="mw-page-title-main">Cure Rare Disease</span>

Cure Rare Disease is a non-profit biotechnology company based in Boston, Massachusetts that is working to create novel therapeutics using gene therapy, gene editing and antisense oligonucleotides to treat people impacted by rare and ultra-rare genetic neuromuscular conditions.

Toshifumi (Toshi) Yokota is a medical scientist and professor of medical genetics at the University of Alberta, where he also holds the titles of the Friends of Garrett Cumming Research & Muscular Dystrophy Canada Endowed Research Chair and the Henri M. Toupin Chair in Neurological Science. He is best known for his studies of antisense oligonucleotide-based therapeutics for muscular dystrophy that led to the development of an FDA-approved drug viltolarsen. His research interests include precision medicine for muscular dystrophy and genetic diseases. He has co-edited two books both published in the Methods in Molecular Biology series from Humana Press, Springer-Nature, and has published more than 100 refereed papers and patents. He is a member of the editorial boards for the International Journal of Molecular Sciences, Genes, Frontiers in Genome Editing, Frontiers in Physiology, and Nucleic Acid Therapeutics, a member of the Medical and Scientific Advisory Committee of Muscular Dystrophy Canada, and a co-founder of the Canadian Neuromuscular Network (CAN-NMD).

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

Ultragenyx is an American biopharmaceutical company involved in the Research and Development of novel products for treatment of rare and ultra-rare genetic diseases for which there are typically no approved treatments and high unmet medical need. The company works with multiple drug modalities including biologics, small molecule, gene therapies, and ASO and mRNAs in the disease categories of bone, endocrine, metabolic, muscle and CNS diseases.

Casimersen, sold under the brand name Amondys 45, is an antisense oligonucleotide medication used for the treatment of Duchenne muscular dystrophy (DMD) in people who have a confirmed mutation of the dystrophin gene that is amenable to exon 45 skipping. It is an antisense oligonucleotide of phosphorodiamidate morpholino oligomer (PMO). Duchenne muscular dystrophy is a rare disease that primarily affects boys. It is caused by low levels of a muscle protein called dystrophin. The lack of dystrophin causes progressive muscle weakness and premature death.

Frederick Sachs is an American biologist. He is a SUNY Distinguished Professor in the University at Buffalo's Department of Physiology and Biophysics.

References

  1. ↑ "H. Lee Sweeney, Ph.D". Perelman School of Medicine at the University of Pennsylvania. Archived from the original on 7 July 2015. Retrieved 18 June 2017.
  2. 1 2 3 "Press Release: Penn Scientist Named First Director of New Center for Orphan Disease Research and Therapy – PR News". Penn Medicine. November 28, 2012.
  3. 1 2 "UF Recruits Muscle Expert". Health News Florida. May 29, 2014.
  4. ↑ Wenner, Melinda (August 15, 2008). "How to Be Popular during the Olympics: Be H. Lee Sweeney, Gene Doping Expert". Scientific American.
  5. ↑ Epstein, David (2013). The Sports Gene: Inside the Science of Extraordinary Athletic Performance. Penguin. pp. 77ff. ISBN   9781101622636.
  6. ↑ Sweeney, H. Lee (July 2004). "Gene Doping". Scientific American. 291: 62–69. doi:10.1038/scientificamerican0704-62.
  7. ↑ Hamilton, Jon (August 12, 2013). "New Muscle Drugs Could Be The Next Big Thing In Sports Doping". Morning Edition, NPR.
  8. ↑ Coghlan, Andy (14 March 2012). "Blood tests won't stop gene cheats". New Scientist.
  9. ↑ DeLessio, Joe (31 March 2015). "Genetic Doping Is the Next Frontier of Cheating in Sports". New York Magazine.
  10. 1 2 Maugh II, Thomas H. (28 April 2007). "Drug may cure genetic diseases". Los Angeles Times.
  11. ↑ "Prof. H Lee Sweeney". Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences - HMA. 2008. Retrieved 18 June 2017.
  12. ↑ "Press release: PTC Therapeutics Announces $15.4 Million NIH Research Grant for Duchenne Muscular Dystrophy | Evaluate". PTC, University of Pennsylvania, and the NIH via Evaluate Group. July 10, 2007.
  13. ↑ Barton-Davis, ER; Cordier, L; Shoturma, DI; Leland, SE; Sweeney, HL (August 1999). "Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice". The Journal of Clinical Investigation. 104 (4): 375–81. doi:10.1172/jci7866. PMC   481050 . PMID   10449429.
  14. ↑ Welch, EM; Barton, ER; Zhuo, J; Tomizawa, Y; Friesen, WJ; Trifillis, P; Paushkin, S; Patel, M; Trotta, CR; Hwang, S; Wilde, RG; Karp, G; Takasugi, J; Chen, G; Jones, S; Ren, H; Moon, YC; Corson, D; Turpoff, AA; Campbell, JA; Conn, MM; Khan, A; Almstead, NG; Hedrick, J; Mollin, A; Risher, N; Weetall, M; Yeh, S; Branstrom, AA; Colacino, JM; Babiak, J; Ju, WD; Hirawat, S; Northcutt, VJ; Miller, LL; Spatrick, P; He, F; Kawana, M; Feng, H; Jacobson, A; Peltz, SW; Sweeney, HL (3 May 2007). "PTC124 targets genetic disorders caused by nonsense mutations". Nature. 447 (7140): 87–91. Bibcode:2007Natur.447...87W. doi:10.1038/nature05756. PMID   17450125. S2CID   4423529.
  15. ↑ "Translarna - Summary of Product Characteristics". UK Electronic Medicines Compendium. 24 April 2017. Retrieved 18 June 2017.
  16. ↑ "H. Lee Sweeney, Ph.D." Cytokinetics. Retrieved 18 June 2017.
  17. ↑ "Lee Sweeney, Ph.D." Solid Biosciences. 6 April 2016. Retrieved 18 June 2017.
  18. ↑ "Scientific Advisory Committee (SAC) - Parent Project Muscular Dystrophy". Parent Project Muscular Dystrophy. Retrieved 18 June 2017.
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