CLINICAL TRIALS
T Cells Suppress Progression of Disease in ALS Patients
David Beers, PhD, Associate Research Professor of Neurology; Stanley H. Appel, MD, Peggy & Gary Edwards Distinguished Endowed Chair, Houston Methodist Neurological Institute
“ We assumed the T cells were detrimental, but it turns out the opposite is true: T cells are protective.
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– Stanley H. Appel, MD
An interdisciplinary team of researchers and physicians at the
Populations of Tregs were also found to be altered in ALS
Houston Methodist Neurological Institute, led by Stanley H.
patients. Patients with rapidly progressing ALS had fewer
Appel, MD, director of the institute and chair of the Stanley
Tregs and consequently, a reduced ability to suppress the
H. Appel Department of Neurology, are investigating the
proliferation of other effector T cells. Surprisingly, when the
etiology and pathophysiology of amyotrophic lateral sclerosis
Tregs were expanded outside the body, they regained their
(ALS). The cause of ALS is elusive.
suppressor function, suggesting they could be reinfused to
More than 30 different genetic determinants of familial ALS
help fight ALS.
have been identified, but sporadic disease with no known
These findings have formed the basis of the first-in-human
mutations accounts for 90 to 95 percent of ALS cases.
FDA/IRB-approved phase I study in which an ALS patient’s
The Edwards ALS Research Laboratory hypothesized that the common culprit in ALS, and a potential target for therapeutic intervention, is neuroinflammation, which is caused by innate immune microglia and adaptive immune T cells. Researchers David Beers, PhD, and Jenny Henkel, PhD, developed an ALS mouse model without T cells, thinking the models would have less neuroinflammation and be protected from developing ALS. Instead, ALS progression worsened, and they discovered that the T cells were protective. In fact,
own Tregs are expanded and then reinfused. The Tregs were reinfused at two different phases of disease – at an early stage and a later stage. Early results showed that reinfusions were safe and well-tolerated. Following infusions, Jason Thonhoff, MD, PhD found that ALS disease progression was slowed during the time of infusions. The trial is a collaboration with Merit Cudkowicz, MD at the Massachusetts General Hospital. The study is sponsored by ALSFindingaCure®, and funded by the Leandro P. Ruzzuto Foundation and GE.
a specific subpopulation of T cells called regulatory T cells
Appel’s ALS patients are the driving force behind the team
(Tregs) that are known to stifle inflammation were able to
and their research. “After all of our hard work over many
suppress ALS progression. Transplanting Tregs into the ALS
years, we are excited about the opportunity to benefit our
models dramatically slowed disease and prolonged survival.
very deserving ALS patients.”
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