Disorders in movement

Date:
August 19, 2020
Source:
DZNE - German Center for Neurodegenerative Diseases
Summary:
Medical researchers are tracking the onset of ataxias. The
results provide valuable data for prevention studies. The data
were collected by a research network, which includes scientific
institutions from Austria, France, Germany, Hungary, Italy, Poland
and Spain.



FULL STORY ========================================================================== Medical researchers are tracking the onset of ataxias. The results
provide valuable data for prevention studies. The data were collected by
a research network, which includes scientific institutions from Austria, France, Germany, Hungary, Italy, Poland and Spain.


========================================================================== "Spinocerebellar ataxias" are diseases of the nervous system associated
with a loss of motor coordination. A European research alliance headed by
the German Center for Neurodegenerative Diseases (DZNE) and the University
of Bonn has now registered whether and how symptoms of ataxia developed
over the years in around 250 persons at risk, who initially did not show symptoms. This is the first study worldwide to investigate the onset of spinocerebellar ataxia directly and in a large group of individuals. The results published in the journal The Lancet Neurology provide valuable
data for prevention studies.

The term "ataxia" -- which is derived from the Greek expression for
"lack of order" -- describes a series of nervous diseases in which the interplay between different muscle groups and, as a result, movement coordination is impaired.

"Ataxia manifests as motor disorders such as gait insecurity and a
tendency to fall. Handwriting becomes blurred and gripping and holding,
for example cutlery, gets difficult. Also, speech can become unclear and blurred," explained Prof. Thomas Klockgether, Director of the Department
of Neurology at the University Hospital Bonn and Director of Clinical
Research at the DZNE.

Slow development Ataxias are among the "rare diseases" and are estimated
to affect around 16,000 people in Germany. Various causes are known for
the associated damage to the cerebellum and spinal cord. So far, however,
it is only possible to alleviate disease symptoms. "Many ataxias are
caused by genetic defects. Other forms of ataxia are acquired and may
be triggered, for example, by immune processes or vitamin deficiencies,"
said Klockgether.

In general, ataxias develop slowly, over years. In the subgroup of "spinocerebellar ataxias," which belong to the hereditary ataxias,
marked symptoms usually do not appear until adult age. "During the presymptomatic phase, nerve damage is still slight. It is assumed that
during this period the chances of influencing the later course of the
disease and possibly slowing it down, that is acting preventively, are
best," Klockgether continued. "In addition to better early diagnosis,
the development of therapies also requires a more precise understanding
of the progression of the disease. This allows identifying time windows
in which a treatment has a chance of success." Largest study so far


========================================================================== Significant findings in this regard are now provided by the largest study
to date on the onset of spinocerebellar ataxias. The data were collected
by a research network coordinated by Thomas Klockgether, which includes 14 scientific institutions from seven European countries (Austria, France, Germany, Hungary, Italy, Poland and Spain). In total, the researchers
studied 252 adults -- all of them children or siblings of people with spinocerebellar ataxia and therefore persons at risk -- to determine how
their movement coordination developed over a period of several years. The study, which started enrolling volunteers in 2008, covers the four most
common types of spinocerebellar ataxia: These are designated SCA1, SCA2,
SCA3 and SCA6 according to international nomenclature.

At the beginning of the study, none of the participants showed
ataxia. However, about half of them were "mutation carriers," i.e. they
had ataxia triggering gene variants. These genetic findings were
anonymised in order not to influence data analysis. About half of the
mutation carriers actually developed symptoms of the disease during
the study period. "For the remaining mutation carriers, this is also
expected. We will continue to monitor the health development of all
study participants," said Klockgether.

Better biomarkers needed The now available results provide precise data
on the progression from the presymptomatic phase to the emergence of
disease symptoms. "Our study now shows that with the established tests
of movement coordination, ataxia can actually not be detected until
the disease is relatively advanced. This would be too late for early intervention. Thus, there is an urgent need for additional biomarkers
that are indicative even before the onset of clinical symptoms," said
Dr. Heike Jacobi, a physician at the University Hospital of Heidelberg,
who shares the first authorship of the current publication with a French colleague. Ideally, readings derived from a simple blood sample would be
the best option. Brain scans could also possibly provide valuable clues, according to Jacobi. "Some of our study participants were examined by
magnetic resonance imaging. We tend to see that in some forms of ataxia
certain regions of the brain shrink even before symptoms of ataxia
manifest. However, since our sample of MRI scans was relatively small,
this effect should be checked in larger study groups." Bases for the development of therapies For prevention studies, the current results
provide valuable information. Such studies are planned in detail. "For
this, it is important to estimate how large a study group needs to be in
order to be able to establish within a certain period of time whether
a new drug is effective. Our findings now provide for the first time
data that allow such a calculation," said Klockgether. About 170 to 270 mutation carriers should be included in such studies in order to be able
to expect a statistically significant delay in the onset of the disease
over a trial period of two years. The exact size of the study group
depends on the type of ataxia. "For the treatment of spinocerebellar
ataxia experimental approaches exist that aim to reduce the effect of the disease-causing gene mutations. The pharmaceutical industry is planning clinical studies on this.

Our results provide important bases for the design of such trials,"
said Klockgether.


========================================================================== Story Source: Materials provided by DZNE_-_German_Center_for_Neurodegenerative_Diseases.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Heike Jacobi, Sophie Tezenas du Montcel, Sandro Romanzetti, Florian
Harmuth, Caterina Mariotti, Lorenzo Nanetti, Maria Rakowicz,
Grzegorz Makowicz, Alexandra Durr, Marie-Lorraine Monin,
Alessandro Filla, Alessandro Roca, Ludger Scho"ls, Holger Hengel,
Jon Infante, Jun-Suk Kang, Dagmar Timmann, Carlo Casali, Marcella
Masciullo, Laszlo Baliko, Bela Melegh, Wolfgang Nachbauer,
Katrin Bu"rk-Gergs, Jo"rg B Schulz, Olaf Riess, Kathrin Reetz,
Thomas Klockgether. Conversion of individuals at risk for
spinocerebellar ataxia types 1, 2, 3, and 6 to manifest ataxia
(RISCA): a longitudinal cohort study. The Lancet Neurology, 2020;
19 (9): 738 DOI: 10.1016/S1474-4422(20)30235-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200819102817.htm

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