Parkinson’s Disease May Have Link to Stroke
Parkinson’s disease: early detection crucial, new therapy approaches on the horizon
24 June 2017
B&K Kommunikation
Detecting Parkinson’s disease
before non-reversible symptoms occur: New approaches to early detection
are meant to ensure just that. They are based on detection of
alpha-synuclein in the skin or intestines. New therapy approaches such
as a potential “vaccination” could improve the prognosis of affected
individuals in future. Prof Günther Deuschl, President of the European
Academy of Neurology (EAN), summarized the latest findings in research
on Parkinson’s’ disease.
New findings on the early detection and
treatment of Parkinson’s disease are being discussed at the 3rd Congress
of the European Academy of Neurology (EAN) in Amsterdam. “We are
getting closer to the big goal of being able to detect Parkinson’s
disease at a very early stage,” said EAN President Prof Dr Günther
Deuschl from University Hospital Schleswig-Holstein in Kiel. The
diagnosis of Parkinson’s disease is difficult particularly in the early
phase of the disease (prodromal stage). Although complaints such as
sleep disorders, loss of smell, bouts of depression or digestive
disorders have been identified as possible early signs of Parkinson’s
disease, diagnosis today cannot be carried out with greater certainty
until the typical movement disorders manifest themselves, such as
tremors and slow, stiff movements. These symptoms are preceded by years
of nerve cells dying off. About 80 per cent of the dopaminergic nerve
endings and as many as 50 per cent of the nerve cells in the substantia
nigra area of the brain are already destroyed by that stage. A therapy
capable of stopping the disease from taking its course is no longer
possible at that point in time. The pathological hallmark of Parkinson’s
disease is the deposit of pathologic alpha-synuclein in cells of the
nervous system.
Early detection with biopsies
Different research groups have reported
biopsies of the skin (Donadio et al., 2016), submandibular glands (Adler
et al., 2016, Vilas et al., 2016) and colon biopsies (Schneider et al.,
2016) showing such alpha synuclein at a very early stage of Parkinson’s
disease. A further major success in early detection was reported
recently (Doppler et al., 2017): Pathologic alpha synuclein was
demonstrated in REM-sleep behavioural disorder, a condition which leads
in about 85 per cent of the sufferers to Parkinson’s disease with the
aid of a skin test – and thus, this is many years before the onset of
the typical movement disorders. The skin biopsy requires taking only a
five millimetre large sample. Detection of pathological deposits of the
protein alpha-synuclein in the fine nerve endings of the skin indicates
the genesis of the disease.
It has long been known that a high
percentage of people suffering from REM sleep behaviour disorders
entailing aggressive dreams and violent movements while sleeping will
contract Parkinson’s within 15 to 20 years. The study has now been able
to identify the biomarker alpha-synuclein in the skin of these patients
at risk. Alpha-synuclein is also found in healthy individuals but is
present in pathological clumped form in Parkinson’s patients. That
results in a malfunction of cell metabolism and ultimately in the
degeneration of nerve cells. Prof Deuschl: “The method has great
potential for identifying patients for Parkinson’s prevention studies
and for winning them over to take part in clinical studies to test
disease-modifying medications.” In future, this diagnostic marker should
be able to detect Parkinson’s disease at an early stage also in
individuals who do not have REM sleep behaviour disorders.
Biomarkers detectable in intestines and salivary glands
However, this is not the only early
detection method that is currently the subject of intensive research.
Pathologic alpha-synuclein aggregations also form in the enteric nervous
system, which consists of the myenteric plexus between the muscle
layers of the intestinal wall and the submucous plexus. The protein
accumulations in this area cannot be viewed automatically as diagnosis
criterion for Parkinson’s disease, however, because they also occur in
healthy individuals. Prof Deuschl: “But if aggregations exhibit certain
patterns, we can distinguish Parkinson’s patients from healthy
individuals with a refined morphometric analysis. Nonetheless, further
studies are needed to prove that Parkinson’s can be diagnosed by means
of gastrointestinal biopsies.” A Spanish study was also able to prove
that alpha-synuclein deposits are detectable by means of a needle biopsy
also in the submandibular salivary glands in patients with REM sleep
behaviour disorders and thus with early signs of Parkinson’s.
New therapies for mitigation of symptoms
New therapeutic approaches rely on
treating the disease already in its early stages and stopping nerve
cells in the brain from dying off. In recent years, experts have gained
an ever better understanding of how Parkinson’s originates and how it
spreads. Prof Deuschl: “Today we know that nerve cells sick from
Parkinson’s disease can ‘infect’ other nerve cells in a manner similar
to prion diseases. The disease gradually spreads in this way throughout
the entire nervous system.” New therapy approaches are being developed
based on this finding. Studies pursue the goal developing a “vaccine”
against Parkinson’s disease and rely on two different strategies in
these efforts: Either stimulate the immune system to generate antibodies
against alpha-synuclein or administer synthetic antibodies.
Another new therapy approach relies on
binding larger quantities of iron. That is because oxidative stress in
the cells also contributes to the development of Parkinson’s disease.
This in turn is caused by excessive amounts of iron in certain regions
of the brain, which accelerate the demise of the cells.
New definition of diagnostic criteria
One important advance in the early
detection of Parkinson’s disease is the new definition of diagnostic
criteria for the prodromal stage, during which the classic diagnosis
based on motor symptoms is not yet possible. To this end, the Movement
Disorder Society drew on clinical studies and statistical studies to
create a criteria list that is meant to standardise the clinical
research and to facilitate diagnosis in the very early stage (Berg et
al., 2015). Prof Deuschl: “The new system for assessing the risk of
Parkinson’s disease consists of the age of the patient, environmental
triggers such as smoking or caffeine consumption, genetic factors, the
results of biomarker tests or prodromal symptoms such as constipation
and loss of smell. This system can be expanded at any time if new tests
are added for early detection – such as skin biopsies for example.”
Parkinson’s disease is second only to
Alzheimer’s as the most frequent neurodegenerative disease of the
central nervous system. Parkinson’s affects about two per cent of the
population over age 65 and is one of the most common neurodegenerative
diseases throughout Europe with 1.2 million people suffering from it.
Estimates indicate that the number of cases might at least double by
2030 due to ever longer life expectancy figures.
Sources: Adler CH, Dugger BN, Hentz JG, Hinni ML, Lott DG,
Driver-Dunckley E, et al. Peripheral Synucleinopathy in Early
Parkinson's Disease: Submandibular Gland Needle Biopsy Findings. Mov
Disord. 2016 Feb;31(2):250-6. Berg D, Postuma RB, Adler CH, Bloem BR,
Chan P, Dubois B, et al. MDS research criteria for prodromal Parkinson's
disease. Mov Disord. 2015 Oct;30(12):1600-11. Donadio V, Incensi A,
Piccinini C, Cortelli P, Giannoccaro MP, Baruzzi A, et al. Skin nerve
misfolded alpha-synuclein in pure autonomic failure and Parkinson
disease. Ann Neurol. 2016 Feb;79(2):306-16. Doppler K, Jentschke HM,
Schulmeyer L, Vadasz D, Janzen A, Luster M, et al. Dermal
phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as
prodromal Parkinson's disease. Acta Neuropathol. 2017
Apr;133(4):535-45. Schneider SA, Boettner M, Alexoudi A, Zorenkov D,
Deuschl G, Wedel T. Can we use peripheral tissue biopsies to diagnose
Parkinson's disease? A review of the literature. Eur J Neurol. 2016
Feb;23(2):247-61. Vilas D, Iranzo A, Tolosa E, Aldecoa I, Berenguer J,
Vilaseca I, et al. Assessment of alpha-synuclein in submandibular glands
of patients with idiopathic rapid-eye-movement sleep behaviour
disorder: a case-control study. Lancet Neurol. 2016 Jun;15(7):708-18.
I am stunned by these new findings.
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