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2014 Volume 26 Number 2
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Understanding Persistence
Columbia University research center pursues a cure for chronic Lyme
By Brian A. Fallon, MD, MPH
The Lyme & Tick-borne Diseases (TBD)
Research Center, established in 2007 at
the Columbia University Medical Center,
benefits from the joint effort of the Lyme
Disease Association, the Lyme Research
Alliance (previously Time for Lyme), and
the trustees of Columbia University. The
mission of the Center is to bring together
a multidisciplinary team of investigators to
study the problem of chronic Lyme disease
(CLD) and to serve as an educational re-
source to the medical community both
locally and nationally. Our focus has been to
understand the mechanisms of persistence
— to examine why patients have persistent
symptoms, to identify biomarkers or tests
that would be helpful in differentiating the
cause, and to identify effective treatments.
One of the great pleasures of this work
has been to collaborate with investigators
withinColumbiaUniversity (such as Armin
Alaedini, Rafal Tokarz, James Moeller,
Serge Cremers, Robert Winchester, Harold
Sackeim) as well as those outside such as
Steven Schutzer, Madeleine Cunningham,
Ben Luft, Tao Liu. Charles Chiu and many
others.
On the research front, most satisfying
has been our work on the neurologic, neu-
ropsychiatric, and neuroimmunologic
aspects of this disease. Research from our
Center has identified several key facts about
chronic Lyme symptoms.
Patients with post-treatment Lyme
disease (PTLD) have objective markers
of persistent illness. We have shown this
through studies of brain blood flow and
metabolism, through studies of immune
markers in the peripheral blood and pro-
teomic studies of the spinal fluid, and
through clinical studies using neurocog-
nitive testing.
PTLD patients have markers that dif-
ferentiate Lyme from Chronic Fatigue
Syndrome and depression. This finding
emerged by proteomic studies of the ce-
rebrospinal fluid and by neurocognitive
studies.
While PTLD has brainmetabolic deficits,
there are also prominent vascular flow
deficits. What appears to unite many of
these findings is an ongoing abnormally ac-
tivated immune response and abnormally
activated brain networks. Why this ab-
errant immune activation and brain acti-
vation persists and how to down-regulate
this response are key questions that shape
our new research efforts. Our former NIH
postdoctoral fellow Dr. Alla Landa, now an
assistant professor at Columbia, is leading a
brain imaging, immunologic and treatment
study of post-treatment Lyme pain to better
understand the Central Sensitization that
appears so problematic to these patients.
We also have a new NIH postdoctoral
fellow who will be establishing a biore-
pository to investigate Lyme-related and
other anti-neuronal antibodies in children,
adolescents and young adults as a potential
cause of severe neuropsychiatric disease.
Testing
We have collaborated with researchers
in the U.S., England, and Germany to help
identify better diagnostic tests for Lyme.
These collaborations are in full swing as we
embarked this year on a prospective diag-
nostic study that has the advantage of col-
lecting samples from patients with new
onset disease from several states and fol-
lowing each of these patients over two
years.
With key collaborators nationally and
internationally, we are investigating several
novel Lyme and co-infection assays —
some PCR based, some antibody-based,
and some cytokine based. Unlike antibody-
based tests, one of the new assays under in-
vestigation appears highly sensitive in de-
tecting active infection within days of the
tick bite and, importantly, may become
negative after the infection has been treated.
If results from our study here in the U.S. are
as promising as studies in Europe, the Lyme
community will have a very useful new di-
agnostic test in the not too distant future to
mark active infection.
Our study is tracking the immune re-
sponse over time and using state-of-the-art
newly developed nationally standardized
clinical assessments to more precisely de-
scribe the clinical profile of PTLD. This will
enable us to explore whether there is a “bi-
Brian Fallon, MD, (far right), and his multidisciplinary team of investigators continue to study
chronic Lyme disease to identify the cause and effective treatments.