Karolinska Institute. Sweden: Scientists at Karolinska Institutet have evaluated a new Alzheimer’s therapy in which the patients receive an implant that stimulates the growth of a certain type of nerve cell. The results, which are published in the journal Alzheimer's & Dementia , suggest that the introduction of a nerve growth factor can prevent neuronal degradation in Alzheimer’s patients.
Patients with Alzheimer’s disease suffer a selective and early
breakdown of so-called cholinergic nerve cells, which require a specific
nerve growth factor (NGF) – essentially a group of proteins necessary
for cell growth and survival – to function. As NGF levels decline, the
cholinergic nerve cells begin to degrade and the patient’s condition
slowly deteriorates.
In an attempt to curb the breakdown of the cholinergic nerve
cells, researchers at Karolinska Institutet’s Centre for Alzheimer’s
Research and their colleagues at
Karolinska University Hospital
’s neurosurgery clinic and the Danish biotech company
NsGene
introduced NGF directly into the brains of Alzheimer’s patients. To
do this, they used NGF-producing cell capsules, placing them in the
basal fore-brain where the cholinergic cells reside using precision
stereotactic surgery. There the capsules, which can easily be removed,
release NGF to the surrounding cells in order to prevent their
degradation.
The study now published in
Alzheimer’s & Dementia
is based on data from six Alzheimer’s patients. To gauge
whether the NGF release had any effect on the cholinergic nerve cells,
the researchers assayed the presence of specific markers of functioning
cholinergic cells. This cell system communicates using acetylcholine,
which in turn produces an enzyme called ChAT (pronounced Cat) that is
found both inside and outside the cells. The team therefore developed a
method enabling them to measure ChAT in the cerebral spinal fluid for
the first time.
“Our results show that when the patients received NGF, there
was a significant increase in ChAT in the CSF,” says Dr Taher
Darreh-Shori, one of the researchers involved in the study. “The
patients that exhibited this increase were also those that responded
best to the treatment. Our PET scans also showed an increase in
cholinergic cell activity and metabolism in the brain.”
In addition, the researchers were able to detect a retardation
of memory impairment over time compared with untreated patients. While
all this suggests that cholinergic functionality improved in the
Alzheimer’s patients who had received NGF therapy, the team adds the
caveat that far-reaching conclusions should not be drawn from the
results:
“The results are promising, but must be treated with
circumspection as only a few patients participated in the study,” says
principal investigator Professor Maria Eriksdotter. “So our findings
will have to be substantiated in a larger controlled study using more
patients.”
The NGF-producing cell capsule method (encapsulated cell
biodelivery) was developed by NsGene. The paper’s first authors are
doctoral students Azadeh Karami and Helga Eyjolfsdottir.. The study was
financed by grants from several sources, including the
Foundation Olle Engkvist Byggmästare, Åke Wiberg’s Foundation,
Åhlén Foundation
, the Swedish Dementia Fund, the Odd Fellows, the King
Gustaf V and Queen Victoria Free Mason Foundation, Karolinska
Institutet’s strategic research programme in neuroscience (StratNeuro),
the Swedish Research Council and Swedish Brain Power (for a full list of
financiers see the published article).
Publication:
'
Changes in CSF cholinergic biomarkers in response to cell therapy with NGF in patients with Alzheimer’s disease
', Karami, A., H. Eyjólfsdóttir, S. Vijayaraghavan, G. Lind, P.
Almqvist, A. Kadir, B. Linderoth, N. Andreasen, K. Blennow, A. Wall, E.
Westman, D. Ferreira, M. Kristoffersen-Wiberg, L. O. Wahlund, Seiger, Å.
, A. Nordberg, L. Wahlberg, T. Darreh-Shori, M. Eriksdotter,
Alzheimer’s & Dementia
, uncorrected proof online 9 February 2015, doi 10.1016/j.jalz.2014.11.008.
For further information, please contact:
Taher Darreh-Shori, pharmacologist, associate professor
Centre for Alzheimer’s Research, division of translational Alzheimer’s neurobiology
Department of Neurobiology, Care Sciences and Society
Tel: +46 (0)8-585 836 12 or +46 (0)708620230
Email: taher.darreh-shori@ki.se
Professor Maria Eriksdotter, senior physician
Centre for Alzheimer’s Research, division of clinical geriatrics
Department of Neurobiology, Care Sciences and Society
Tel: +46 (0)70-647 8907
Email: maria.eriksdotter@ki.se