open access: Nature Reviews: Key Advances in Medicine

NEUROLOGY
levels of auto antibodies against α-synuclein,
the main component of Lewy bodies, in the
serum of patients with PD in early and late
stages of the disease. Significantly higher
auto antibody levels were found in patients
than in controls, but the antibody response
decreased as the condition became more
advanced. The authors interpreted this
find ing in the context of a protective role for
auto immunity in PD that seems to be stronger
in the early phases of the disease, and
may be of value as a biomarker, especially at
this crucial stage of PD pathogenesis.
‘‘ …the treatment of PD has
been limited to symptomatic
drug therapy and deep brain
stimulation
In the absence of neuroprotective therapies,
the treatment of PD has been limited
to symptomatic drug therapy and deep
brain stimulation. To explore the potential
of gene therapy, LeWitt and colleagues
performed the first double-blind, shamsurgery-
controlled, randomized trial of
in vivo gene transfer in patients with PD. 9
The investigators used adeno-associated
viral vector (AAV2) for transduction of
the gene encoding glutamic acid decarboxylase
(GAD), an enzyme that catalyzes
the decarb oxylation of glutamate to
γ-aminobutyric acid and is expected to
increase the inhibitory tone in the basal
ganglia. The trial involved 55 patients aged
30–75 years with levodopa-responsive
PD, who were randomly assigned to sham
surgery (n = 23) or AAV2–GAD infusions
(n = 22) at baseline.
At the 6-month study end point, 21 and
16 patients were assessed in the shamtreated
and gene-therapy groups, respectively.
The mean Unified Parkinson’s
Disease Rat ing Scale (UPDRS) motor score
was found to have decreased by 8.1 points
(23.1%) in the AAV2–GAD group and
by 4.7 points (7.0%) in the sham group. 9
’’
Over all, the study is encouraging, since the
group dif ference was highly significant and
no serious adverse events were observed in
either group. Caveats of this study include
rela tively small group sizes, a heterogeneous
patient population in terms of age of onset,
more-severe dis ease in the sham group,
limited dis criminatory power of the UPDRS
(maximum 108 points) in the lower range,
and the relatively short follow-up period.
In conclusion, these studies highlight the
importance of identifying the molecular
underpinnings of disease pathways to
uncover therapeutic targets. The discovery
of genetic mutations in these pathways has
sug gested converging mechanisms in the
patho genesis of movement disorders. In
order to rapidly translate research advances
into the clinic, it is critically important to
iden tify markers of disease progression,
especially in individuals who are at risk of
developing a neurodegenerative disease.
Department of Neurology, University of Lübeck,
Ratzeburger Allee 160, 23538 Lübeck,
Germany (C. Klein). Department of Neurology,
Massachusetts General Hospital, Harvard
Medical School, 114 16 th Street, Room 2007,
Charlestown, MA 02129, USA (D. Krainc).
Correspondence to: C. Klein
christine.klein@neuro.uni-luebeck.de
Acknowledgments
C. Klein is funded by a career development award
from the Hermann and Lilly Schilling Foundation.
D. Krainc is supported by the National Institute of
Neurological Disorders and Stroke and the
CHDI Foundation.
Competing interests
The authors declare no competing interests.
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sera of Parkinson’s disease patients. PLoS ONE
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MULTIPLE SCLEROSIS IN 2011
Advances in therapy, imaging
and risk factors in MS
Bianca Weinstock–Guttman and Murali Ramanathan
Multiple sclerosis research in 2011 produced a combination of new
therapeutic developments and innovative findings. Teriflunomide showed
beneficial effects in a phase III trial, quantification methods for MRI
lesions that should improve monitoring of disease progression were
devised, and a link between high cholesterol and low vitamin D emerged.
Weinstock–Guttman, B. & Ramanathan, M. Nat. Rev. Neurol. 8, 66–68 (2012); published online 10 January 2012;
doi:10.1038/nrneurol.2011.213
For multiple sclerosis (MS), the research
milestones of 2011 were a combination of
new therapeutic developments and innovative
findings that might help to explain the
heterogeneity in both disease progression
and responses to therapy in patients with
MS. The new oral therapy teriflunomide
showed beneficial effects in a large phase III
clinical trial, 1 which provides hope for better
and more-convenient control of MS in the
future. The identification of new methods
to quantify cortical lesions on MRI will
improve our ability to monitor disease progression,
2 and studies have identified raised
cholesterol and reduced vitamin D levels as
detrimental factors in patients with MS. 3,4
From a therapeutic standpoint, 2011
will be remembered as a defining year
for MS. Following a successful clinical
trial, reported in 2010, 5 fingolimod—an
oral disease-modifying therapy for MS—
received regulatory approval and became
available to patients in over 50 countries
including the USA, the European Union
and, most recently, Japan. The results from
a phase III clinical trial of teriflunomide
(another oral therapy for MS) were published
in October 2011 in The New England
Journal of Medicine. 1 Teriflunomide is the
active metabolite of leflunomide, which
is already approved for the treatment of
patients with rheumatoid arthritis, and it
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