The new findings could lead to less expensive and more effective ways to treat the disorder, which affects about 1 in 50,000 people in the general population. Those of Eastern and Central European (Ashkenazi) Jewish heritage are at highest risk for the disease, with 1 in 750 affected. The results are published in the October 18 issue of Proceedings of the National Academy of Sciences.
Treatment for Type 1 Gaucher disease—the type that does not cause a rare and fatal neurodegenerative childhood disease—involves expensive recombinant enzyme infusions every two weeks for life, which on average cost $200,000 per year. Gaucher disease symptoms are unpredictable, even among affected siblings. "In order to tailor treatment to individuals, we need an improved understanding of the disease mechanisms," said senior author of the study, Pramod Mistry, M.D., professor of pediatrics and internal medicine at Yale School of Medicine.
For almost 20 years, investigators around the world have tried and failed to develop mouse models of Type 1 Gaucher disease that replicate the human disease faithfully. Mistry and his team were able to develop a mouse model that replicates all of the features of the human disease.
It was previously thought that the disease affects only one cell type in the body called macrophages. "In our study we show that all cell types are involved and lipids that accumulate trigger abnormal signaling resulting in the malfunction of many cell types," said Mistry. "This helps explain aspects of the disease, such as osteoporosis, cancer risk, and risk of Parkinson's disease, all of which did not respond to macrophage-directed enzyme therapy. With this knowledge, we can look forward to developing treatments that are directed not only to macrophages, but to all cell types involved in the disease process."
Mistry and his team have just started enrolling patients in an international trial of a small molecule substrate inhibitor—in the form of a pill, which was developed by Genzyme Corporation. "Because it is a pill and will affect all cell types, we expect it to reverse all, not just part, of the disease. Also, it should be less expensive than enzyme treatment," he said.
The work of a researcher in this study was partially funded by the Yale Clinical and Translational Science Award (CTSA) grant from the National Center for Research Resources at the National Institutes of Health.
Other authors on the study include Jun Liu, Mei Yang, Timothy Nottoli, James McGrath, Dhanpat Jain, Kate Zhang, Joan Keutzer, Wei-Lein Chuang, Wajahat Z. Mehal, Hongyu Zhao, Aiping Lin, Shrikant Mane, Xuan Liu, Yuan Z. Peng, Jian H. Li, Manasi Argawal, Ling-Ling Zhu, Harry C. Blair, Lisa J. Robinson, Jameel Iqbal, Li Sun and Mone Zaidi.
Citation: PNAS doi/10.1073/pnas
Karen N. Peart | EurekAlert!
Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
19.07.2018 | Life Sciences
19.07.2018 | Earth Sciences
19.07.2018 | Social Sciences