Supporting medical research leading to a cure for EM is a core mission of TEA. Since its founding in 1999, TEA has raised money for its Research Fund, which is restricted to use for research.
Dr. Drenth and colleagues in 2001 had identified the gene—SCN9A—linked to EM on chromosome 2. They later confirmed its role in EM by finding mutations to the gene in six families with inherited EM. Dr. Drenth’s 2006 study looked into why variations in one gene explain inherited EM in some people, but other families with EM don’t carry the same genetic mutation. Read an explanation written by Dr. Drenth on page one of FootSteps, June 2007.
The year 2004 was significant for TEA—the year when the dream of actually funding research into EM became reality. TEA donated $60,000 to help fund research into inherited EM at Yale University’s Center for Neuroscience and Regeneration Research under the direction of Stephen G. Waxman, M.D., Ph.D., then chairman of the Department of Neurology at Yale’s School of Medicine.
TEA first helped these neuroscientists by asking members with inherited EM to send samples of their blood to the Yale laboratories. Using state-of-the-art molecular biological technology to analyze DNA from the blood, the researchers found a mutation in the gene (SCN9A) that had been linked to EM in earlier studies. The mutation the neuroscientists identified is in a sodium channel (Nav1.7) found along the length of nerve fibers. It acts as a molecular battery generating and transmitting nerve signals. The researchers demonstrated that the genetic mutation causes the pain of inherited EM by causing pain-signaling nerve cells to be over-excitable, firing when they should not and causing pain. You can read more about this on page one of FootSteps, December 2004.
In 2005, TEA funded a $30,000, one-year grant for a study by Joost PH Drenth, M.D., Ph.D., Radboud University, Nijmegen, The Netherlands. Awarded through the National Organization for Rare Disorders, the grant was administered and monitored by NORD. You can read more about this on page one of FootSteps, December 2005.
Two research papers published by Dr. Drenth and colleagues in 2005 about five families with inherited EM are summarized by TEA member and scientist Jean Jeffery on page three of FootSteps, Fall 2007.
In 2006, the Yale researchers reported another significant discovery. They demonstrated how a single genetic mutation causes not only the pain of inherited EM but also the redness. They showed that a single mutation can produce opposing effects depending on the nerve cells in which it operates, and thus can produce multiple symptoms. Researchers showed the EM genetic mutation (that results in a defect in the sodium channel Nav 1.7) causes over-excitability in one type of neuron (nerve cell) and under-excitability in another type of neuron. Read more about this on page seven of FootSteps, June 2006.
In 2006, TEA announced that the research groups at Yale and in The Netherlands were collaborating on some new studies. These two research programs, along with the program directed by Yong Yang, M.D., Ph.D., in Beijing, China, are the world leaders in research into inherited EM. Helped by TEA’s donations, these highly specialized molecular biological laboratories made enormous strides. Read more on page one, FootSteps, December 2006.
In the same story in FootSteps, June 2007, Dr. Drenth summarized the value of TEA’s donations to research: “The fruits of the research funded by TEA are multifold. Funding research has not only resulted in better understanding of the causes of EM, but also has also shifted the disease into the spotlight and put EM on the agenda of many laboratories. Testament to this are the recent discoveries of two other disorders caused by Nav1.7. One painful disorder (paroxysmal extreme pain disorder) enhances Nav1.7 function, while the second is characterized by the complete absence of pain sensation. Had the researchers who discovered these facts not known about EM and Nav1.7, it would have taken them many years to solve their puzzles. Lastly, big pharmaceutical companies have now begun a search for a drug that specifically blocks Nav1.7 and alleviates the pain. And this is what we really want.”
Drs. Drenth and Waxman co-authored an article summarizing the recent, major advances in EM research that was published in December 2007. Read “Collaboration Results in EM Research Review,” page two, FootSteps, Winter 2008
In 2007, Dr. Waxman’s group began an active collaboration with Dr. Yang, who directs another group of EM researchers in Beijing. Among other accomplishments, Yale’s published work was sparking much interest within the pharmaceutical industry toward the search for drugs that can target mutant Nav1.7 in EM. Read “Research Review,” FootSteps, Winter 2008, page 2.
In 2008, TEA donated $45,000 to Yale, restricting use of the donation to support collaborative efforts with scientists from China and The Netherlands. For two years, Yale hosted Dr. Yang as a visiting scientist working directly with Yale EM researchers. These collaborations pursued new avenues in EM research, including study of factors that increase or decrease an individual’s susceptibility to chronic pain. Read about TEA’s donation and “What TEA’s Gift Will Do,” on pages one and two of FootSteps, Spring 2008.
In 2009, some researchers at Yale analyzed mutations to the EM gene in people who reacted differently to certain drugs like lidocaine. The findings of these studies point the way toward personalized, genetically based treatments. Another study showed mutations that relate to severity of the disorder act differently in a teenager than those who first develop symptoms of inherited EM under the age of ten. Other studies found a common genetic variation in Nav 1.7 that may increase susceptibility to pain. Read more about these findings in “Research Update,” page 3, FootSteps, June 2010.
In 2010, a small pharmaceutical company asked Dr. Drenth to act as principal investigator for clinical trials of a drug they developed to ease the pain of inherited EM. One trial with four people was held in June 2010 with encouraging results but some side effects noted as severe. The company ended the trial to pursue an improved backup drug. Read more about this on page one both the June and November issues of FootSteps, 2010.
Click here to read about Yale's latest research update as produced by Dr. Stephen Waxman's research team.