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Scientific Achievements

Scripps Research Institute scientists have led numerous seminal studies. To highlight only a few of these as an example of their extraordinary work, over the last decades the institute’s investigators have made breakthroughs in studies of:

  • ALZHEIMER’S DISEASE, finding diverse genomic changes in single neurons from the brains of Alzheimer’s patients, pointing to an unexpected factor that may underpin the most common form of the disease. (Chun lab, 2015)
  • HIV/AIDS, creating a novel drug candidate so potent and universally effective, it might work as part of an unconventional vaccine. In other work toward an AIDS vaccine, researchers have made a number of breakthroughs in elucidating the structure of human antibodies that neutralize many different strains of HIV. (Farzan lab, 2015; Wilson, Burton labs (with Ollmann Saphire), 2001 – 2014).
  • CANCER, inventing a new method to disrupt the function of MYC, a regulator involved in a majority of cancers that had been thought to be “undruggable.” (Janda lab, 2014)
  • EBOLA, identifying weak spots on the surface of Ebola virus that are targeted by the antibodies in ZMapp, the experimental drug cocktail administered to several patients during the recent Ebola outbreak. (Ollmann Saphire, Ward labs, 2014)
  • ADDICTION, providing evidence that the drug gabapentin is safe and effective in treating alcohol dependence. The medication, which is already approved by the U.S. Food and Drug Administration for treating seizures and pain, is the only medication shown to support abstinence and improve sleep and mood in people who are eliminating or reducing their alcohol intake. (Mason lab, 2013, clinical trial results; Roberto, Koob, Siggins labs, 2008)
  • PARKINSON’S DISEASE, producing the first known compound to show significant effectiveness in protecting brain cells directly affected by the disease. Multiple labs at TSRI are involved in the effort to find new therapeutic strategies for the disease. (LoGrasso lab, 2011; etc.)
  • MULTIPLE SCLEROSIS AND ULCERATIVE COLITIS, first discovering and synthesizing a drug candidate RPC1063 currently in late-stage clinical trials for these diseases. RPC1063 also has potential for treating other autoimmune disorders. (Rosen, Edwards labs in conjunction with the Scripps Florida Molecular Screening Center, 2000s.)
  • REGENERATIVE THERAPY, reporting a breakthrough in which scientists successfully created live mice from mouse skin cells, without using embryonic stem cells or cloning techniques that require eggs. This milestone opens the door to the development of exciting therapies, such as using a patient's own cells to grow replacement organs. (Baldwin lab, 2009)
  • DEAFNESS, elucidating the action of a protein, harmonin, which is involved in the mechanics of hearing. Defects in such genes can cause devastating diseases, such as Usher's syndrome, which is characterized by deafness, gradual vision loss, and kidney disease. (Mueller lab, 2009)
  • HUNTINGTON'S DISEASE, developing an agent that reversed Huntington’s disease symptoms in mice, with minimal toxicity. (Thomas, Gottesfeld labs, 2008)
  • BLINDNESS, achieving complete inhibition of new blood vessel growth in animal models of neovascular eye diseases and a vascular brain tumor with little or no effect on normal tissue. (Friedlander lab, 2007)
  • AMYLOID DISEASE, developing the first disease-modifying agent targeting the underlying cause of this type of disorder, a class that includes Alzheimer’s disease. A drug based on this finding (tafamidis by FoldRX/Pfizer, Inc.) has been approved for use in Europe to treat a type of inherited disease known as Transthyretin amyloidosis. (Kelly lab, 2003)
  • REVOLUTIONARY CHEMICAL METHODOLOGY, inventing “click chemistry,” a powerful and original new approach to drug design in which the chemical components used "click" together to bind as easily and reliably as the two pieces of a seatbelt buckle.  The buckle works no matter what is attached to it as long as the two pieces can reach one another. TSRI chemists continue to contribute transformative methodology—including creating a powerful new chemical toolkit that radically simplifies the creation of potential new drug candidates and inventing better ways to build organic molecules. (Sharpless lab, 2002; Baran lab, 2012; Yu lab, 2014, etc.)
  • UNNATURAL AMINO ACIDS, creating forms of bacteria and yeast with a genetic code that uses unusual amino acid building blocks to synthesize proteins—in addition to the 20 found in nature. Beyond its theoretical importance, the work provides scientists with a powerful new tool for research as well as for creating new protein therapeutics. More recently, TSRI scientists also created the first living organism that transmits added letters in the DNA “alphabet.” (Schultz lab, 2001; Romesberg lab, 2014)
  • RESPIRATORY DISTRESS SYNDROME, synthesizing surfactant, a lung material that keeps air sacs open and prevents respiratory distress syndrome, a major killer of premature babies. In 2012, a therapy based on this technology (lucinactant/Surfaxin, Discovery Laboratories) was approved by the U.S. Food and Drug Administration. The therapy also has potential to help people suffering from cystic fibrosis, acute lung injury and acute asthma. An aerosolized version is currently under development. (Cochrane lab, work from the 1990s)
  • CANCER DRUG SYNTHESIS, completing the total synthesis of the anti-cancer drug Taxol®, approved by the Food and Drug Administration for the treatment of ovarian cancer. Before the synthesis, Taxol®, whose active compound was first isolated from the bark of the rare Pacific yew, demonstrated great promise as a cancer treatment, but its full impact was prevented by the problem that treating one patient required the destruction of more than three of these precious trees. Also a remarkable feats in synthesis: developing an inexpensive new method for economically synthesizing cortistatin A—a steroid, isolated from a marine sponge, that has shown promise for conditions ranging from macular degeneration to cancer. (Taxol®, Nicolaou lab, 1994; cortistatin A, Baran lab, 2008)
  • GAUCHER'S DISEASE, cloning the gene for the enzyme that is deficient in people with the potentially fatal inherited disorder, and developed a method to predict the severity of the disease. (Ernest Beutler lab, 1991)
  • DRUG DEVELOPMENT TECHNOLOGY LEADING TO TWO APPROVED DRUGS—adalimumab (Humira®), a best-selling treatment of rheumatoid arthritis and other intractable autoimmune diseases, and Belimumab (Benlysta®), a treatment for lupus which, when approved, was the first new therapy for this chronic inflammatory disease in 50 years. The technique—called “combinatorial antibody library technology”— provides a way to identify human antibodies—secreted proteins that help the body clear infections—that might be used therapeutically. By searching among billions of antibody variants taken from human blood samples, the method enables scientists to identify human antibodies that bind to a particular target involved in a particular disease. (Lerner lab, work from the 1980s; Humira® approved to treat rheumatoid arthritis (2002), psoriatic arthritis (2005), ankylosing spondylitis (2006), Crohn's disease (2007), plaque psoriasis (2008), juvenile idiopathic arthritis (2008), moderate-to-severe ulcerative colitis (2012); Benlysta® approval, 2011).
  • CATALYTIC ANTIBODIES, pioneering the development of these molecules (also called “abzymes”)—antibodies that function as enzymes in catalyzing specified chemical reactions, a method thought impossible using classical techniques. This work has yielded insights into reaction mechanisms, enzyme structure and function, catalysis, and the immune system itself, as well as opening up a new approach to drug design for cancer and other diseases. (Lerner, Schultz labs, 1988)
  • HEMOPHILIA, developing a method to purify Factor VIII, a coagulation protein lacking in people with hemophilia A. Use of the purified concentrate greatly reduces the risk to hemophiliacs of infection from blood-borne AIDS, hepatitis, and other viral infections. (Zimmerman lab, 1982)
  • LEUKEMIA, first developing and successfully tested the anti-leukemia drug 2-CdA (approved by the Food and Drug Administration in 1993 and marketed under the name cladribine (Leustatin®) by Ortho Biotech, Inc., an affiliate of Johnson & Johnson). An intravenous medication with remarkably few side effects, 2-CdA now cures or produces many years of freedom from hairy cell leukemia in almost all those receiving treatment. (Carson lab work, late 1970s).

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Drugs From TSRI Discoveries:
Humira® for rheumatoid arthritis and other autoimmune diseases
Surfaxin® for infant respiratory distress syndrome
Leustatin® for hairy cell leukemia
Benlysta® for lupus
Factor VIII for hemophilia
Vyndaqel® for TTR-FAP

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