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Packard Center for ALS Research at Johns Hopkins

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ALS Alert Newsletter | March

Packard Scientists Gather in Baltimore for the 2013 Annual Symposium

The Packard Center's Annual ALS Research Symposium, held last month in Baltimore, held true to its mission of open sharing, a cornerstone of the Center's collaborative model.

Jeff Rothstein, Packard's Medical Director, shares his thoughts at the symposium.

Earlier this month, nearly 150 researchers, postdocs, and graduate students gathered in Baltimore’s Inner Harbor for the annual Packard symposium. At the meeting, scientists from Packard, P2ALS, and NEALS (the NorthEast ALS Consortium) shared their latest results, many times before they had been officially published in research journals.

Such open sharing of results is one of the cornerstones of the Packard Center. Attendance at the annual symposium is required of all Packard grantees, and researchers travel from all over the world to be present. Besides simply sharing their research, the scientists also have the opportunity to forge new connections, to engage in rigorous discussion about each other’s work, and to refine ideas and experiments.

2013 Packard Symposium

“It is always refreshing and rewarding to see how much work has been done in a year and, more importantly, how people come together in a collaborative way to share new ideas for new experiments. This is the goal for us: forging these collaborations between researchers and also with clinicians to hopefully fast-track creation of better and more defined tools to test drugs,” said Packard Science Director Piera Pasinelli.

Packard scientists and others presented a variety of fresh and exciting research that helps us better understand and potentially treat ALS. From neurobiology to treatment trials, scientists discussed virtually every aspect of ALS.

Many of the researchers updated the field on their studies of a variety of neural cells. Besides motor neurons, cell types like astrocytes and oligodendroglia are now believed to play a significant role in the development and progression of ALS. Packard scientists, who were the first researchers to describe the role of these cells in ALS, are now gaining a better understanding of how astrocytes and oligodendrocytes support motor neurons in healthy individuals and determining which aspects of this functioning goes awry in ALS patients.


The importance of astrocytes and oligodendroglia is also reflected in the growing number of treatment trials that are specifically targeting these cells. Although these treatments are primarily still in animal models at this point in time, they point to the potential promise in normalizing these cellular functions.

Other scientists homed in on specific genes rather than specific cell types. The two most frequently discussed genes were, not surprisingly, SOD1 and TDP43. Because these two genes were some of the first genes linked to ALS, they have been the most studied. Researchers are attempting to sort out precisely how these mutations lead to disease. One way they are attacking the problem is by using various methods to reduce aggregations of mutant proteins and see which cellular functions are restored.

The prion-like domains of these proteins also received some attention. Although ALS isn’t a prion disease (like mad cow disease), SOD1, TDP43, FUS, and other proteins linked to ALS have what’s known as a prion-like domain. These domains have two different shapes: a normal shape, and a disease-related one that causes the proteins to stick together and form large clumps. Researchers are looking into the importance of these domains and how the aggregates might lead to disease.  If these genes work like prions, it could help explain how ALS spreads in the body.


The discovery of the repeat expansion in the C9orf72 gene a year and a half ago by Packard scientist Bryan Traynor and colleagues has continued to make waves in the ALS field. Researchers wasted no time in digging into the mechanisms by which the mutant gene or the repeat expansion itself might contribute to disease. Creating good animal models for other diseases caused by genes with repeat expansions has been difficult, but that hasn’t stopped Packard researchers from tackling the problem head-on.

Similar to what they are doing with SOD1 and TDP43, researchers are attempting to alter how much of the C9orf72 protein is produced in cell cultures and animal models to see what effects this might have on cell function and the development of ALS. This will also help scientists understand whether C9orf72 repeat expansion causes disease by interfering with the normal function of the protein (known as a toxic loss-of-function), by actively causing harm (a toxic gain-of-function), or both.

This year, several new genes joined the discussion. Packard scientist J. Paul Taylor, of St. Jude Children’s Research Hospital, recently published a paper in Nature that identified two new genes linked not only to familial ALS but also a suite of muscle, brain, and bone diseases. Together, these diseases are known as multi-system proteinopathies, and understanding how these diseases are linked may help scientists understand the array of symptoms that can accompany ALS.


Scientists from Packard, P2ALS, and NEALS also presented new ways of detecting the changes that accompany disease progression. Usually, researchers and physicians use patient-reported changes in functioning in human studies. In animal studies, it gets even trickier and scientists have to use proxy measurements of ALS progression. Now, researchers are working to develop an array of non-invasive tools to measure ALS symptoms in both humans and animals. These are important not just to determine the severity of illness, but also for measuring drug efficacy during clinical trials.

Despite disappointment over the failure of dexpramipexole to slow ALS progression in Phase III clinical trials, researchers have soldiered on, testing a variety of new ALS drugs and treatments. Many of these drugs, including antibiotics and medication for heart failure, are already FDA-approved for other purposes, which can speed up the process of bringing these drugs to market. Most of the drugs discussed at the symposium were in very early stages of testing, in which researchers were assessing safety and tolerability rather than efficacy.

Although many gene therapy and stem cell therapy trials are still being conducted in animals (and are thus not yet ready to be tested in humans), Packard scientists showed that significant progress was being made. Researchers are injecting genetically modified adeno-associated viruses (AAVs) into mice and rats to either turn down the unhealthy functions of mutant genes or to provide a working gene that has been disabled by the mutation. Preliminary results appear successful in rodents, although it remains unclear if and how these will translate in humans.

The symposium’s keynote speaker, Brian Popko, spoke of his work on oligodendroglia and the myelination process in multiple sclerosis. In MS patients, neurons are repeatedly myelinated and demyelinated, which puts inflammatory stress on the cells. Since problems with oligodendroglia have been noted in ALS, along with increased inflammation, a better understanding of this process in MS could ultimately help ALS patients.

After 2.5 days of non-stop meetings and science, the 2013 Packard symposium was adjourned until next year.  But the work does not stop—Packard scientists will have many new discoveries in the upcoming year that will help us better understand ALS and move closer to developing effective treatments.

Carrie Arnold


ALSO In this Issue

Diane's Dream
Longtime Packard Board member Diane Winokur establishes new research initiative to honor her family’s legacy.

7th Annual Fiesta 5K is right around the corner!
Lace up your running shoes and get ready for the Packard Center's 7th Annual Fiesta 5K for ALS Research on Saturday, May 4, 2013 at Power Plant Live! in downtown Baltimore!

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