New Target For Epilepsy - C&EN Global Enterprise (ACS Publications)

Mar 23, 2015 - For about one-third of patients with epilepsy, existing drugs do little to relieve symptoms such as chronic seizures. When they do work...
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NEWS OF THE WEEK

CONGRESS: Lawmakers pass bills that

would alter agency advice, use of data

T

HE HOUSE OF REPRESENTATIVES has passed

two controversial bills targeting how EPA uses scientific data and receives scientific advice in order to regulate. If the measures survive Senate votes, they would surely face White House vetoes. One bill, H.R. 1030, would bar EPA from using any scientific studies, including clinical health research, as it crafts regulations unless it releases all underlying data for public review. Critics say this would hobble the agency in setting health-protective regulations, such as Clean Air Act standards, because key data are protected by patient confidentiality rules. The House passed the legislation on a vote of 241-175 on March 18. The other measure, H.R. 1029, would mandate that EPA retain more industry panelists for its external Science Advisory Board (SAB). It also would require that 10% of SAB members be representatives from state, local, or tribal governments. The House passed the bill on March 17 on a vote of 236-181.

NEW TARGET FOR EPILEPSY NEUROSCIENCE: Inhibiting metabolic

pathway suppresses seizures in mice

F

OR ABOUT ONE-THIRD of patients with epilepsy,

existing drugs do little to relieve symptoms such as chronic seizures. When they do work, these drugs stop neurons from becoming overexcited by targeting ion channels and other receptors on the cells. Now, researchers in Japan report a novel antiepilepsy target outside neurons. The team demonstrates that inhibiting a metabolic pathway in neuron-helper cells called astrocytes can suppress seizures in mice. “This is a major discovery that will revolutionize the field,” says Detlev Boison, the director of neurobiology at Legacy Research Institute in Portland, Ore., who was not involved in the study. “This study shows that there are other ways to look at treating epilepsy.” The new target is the enzyme lactate dehydrogenase (LDH). It plays a role in how brain cells generate energy from glucose. In one part of the process, astrocytes use enzymes, including LDH, to turn glucose into lactate, which they then shuttle to neurons. The nerve cells convert lactate to pyruvate, which enters the citric acid

The U.S. Chamber of Commerce and other industry groups support both bills. Democrats, environmental groups, and 42 universities and scientific organizations—including the American Chemical Society, the publisher of C&EN—say the bills would pose burdensome new requirements on the agency and research scientists. The White House says the SAB measure “would weaken the scientific independence and integrity” of EPA and its SAB by imposing quotas based on affiliation rather than scientific expertise. Former SAB director Terry F. Yosie, now with the World Environment Center, an international sustainable development organization, says the bill “is a waste of taxpayers’ money and negates the very objectives it purports to serve.” The U.S. Chamber of Commerce says H.R. 1029 “would establish requirements that SAB members are qualified experts” and “that the views of members—including dissenting members—are available to the public.” As the Senate takes up the measures, Democrats say EPA has no resources to cover the $250 million a year the Congressional Budget Office estimates it would take to implement the publicly available science bill.—STEVEN GIBB

Two bills moving through Congress would alter the ways science informs EPA policy-making, affecting air quality standards and other regulations.

SHUTTERSTOCK

HOUSE TAKES AIM AT EPA SCIENCE

cycle, a major metabolic pathway that produces chemical energy for the cell. Tsuyoshi Inoue of Okayama University and colleagues focused on inhibiting LDH because some epileptic patients find relief from seizures when they switch to a low-carbohydrate, high-fat diet that makes brain cells skip the LDH-driven astrocyte process. This ketogenic diet forces the brain to switch from burning glucose to burning fat metabolites called ketone O O bodies, which get pushed directly into the citric acid cycle. The researchers found that blocking LDH directly mimics the ketogenic diet’s effects (Science 2015, DOI: 10.1126/science.aaa1299). When they injected an LDH inhibitor into the hippocampus HO of mice with epilepsy-like symptoms, they observed fewer high-voltage spikes, a cellular sign of seizures, than seen in mice receiving a saline Stiripentol injection. The Okayama team also found that an antiepileptic drug used in Europe called stiripentol inhibits LDH, although that was not part of the molecule’s design. The researchers tested an analog of the compound, isosafrole, and found it was a better LDH inhibitor and suppressed high-voltage spikes to a greater degree compared with stiripentol. The scientists think compounds such as isosafrole could lead to new treatments for drug-resistant epilepsy.—MICHAEL TORRICE

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MARCH 23, 2015

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Isosafrole