MPBD: Therapy
Treatment for neurodegenerative diseases the effects are mostly temporary, and have a lot
• Symptomatic treatment of side effects.
• Disease modifying
Symptomatic treatment for Parkinson’s disease
Symptomatic treatments A successful treatment is the stimulation of
Affect symptoms but not the cause of the dopaminergic transmission with Levodopa (L-
disease. This includes sleep medication, anti- dopa), which is converted to dopamine within the
depressants, anti-anxiety, and substituting lost brain.
neurotransmitter systems (supply
neurotransmitters to gain the function of
neurons back).
Symptomatic treatment for Alzheimer’s
disease
One of the treatments includes stimulation of
cholinergic transmission. This is based on the Side effects of L-Dopa
fact that in Alzheimer’s disease some of the
cholinergic neurons are lost. This is usually
done by inhibiting an enzyme called
acetylcholinesterase that degrades
acetylcholine in the synaptic cleft, thus
inhibition of this enzyme leaves more
acetylcholine in the synaptic cleft.
Deep brain stimulation
This is a form of non-pharmacological
symptomatic treatment where there is a
Another symptomatic treatment is blocking restoration of neurotransmitters.
the NMDA receptor. This causes inhibition of
glutamate excitotoxicity. This is based on when Stem cell treatment
neurons degenerate they release glutamate. This is also a form of non
pharmacological symptomatic
treatment to restore the
neurotransmission.
Though, after a while, there is a
neuroinflammatory response that works against
the transplantation of these cells, which
contributes to the disease.
Most of the time these treatments are given in
the stages where the disease has already
severely progressed. The treatments are also
limited to a certain group of patients and
, Epidemiological studies showed that the risk number of patients
for Alzheimer’s disease was reduced in people Phase 3: Placebo and/or standard comparator on
that are taking non-steroid anti-inflammatory efficacy and tolerability in a large number of
drugs (NSAIDs, ibuprofen) at high dosages and patients
for a very long time. Phase 4: Continued studies in normal clinical
practice: drug surveillance systems,
Inhibition of the inflammatory response observational studies.
Clinical trial outcome measures are biomarkers
and clinical measures (are the symptoms
Unfortunately, most of the traits with NSAIDs improving?)
showed no evidence for efficacy in Alzheimer’s
disease. The targets of NSAIDs in Alzheimer’s Biomarkers
also affect other cell types such as: • Dopamine transporter PET scan or plaque PET
scan. You can look at this over time, after
treatment, etc.
• Cerebro-spinal fluid (CSF) via a lumbar
puncture. CSF is produced by the choroid plexus
of each ventricle.
CSF diagnosis of Alzheimer’s disease
But why was this included in the
epidemiological studies but not in the clinical
trials? Maybe the positive effects were nog by
anti-inflammatory mechanisms, or they
started it too late and there has already been
an accumulation of Aβ and Tau or it could also
be that it inhibits the good inflammatory
response.
It is based on the levels of Aβ42, Tau, and pTau
Disease-modifying (treatment options) proteins. What is kind of surprising is that Aβ42
• Inhibition of formation of aggregating decreases in the CSF and Tau and phospho Tau
proteins increase. This relates to where these proteins are
• Inhibition of aggregation in the brain. In Alzheimer’s disease Aβ42
• Clearance of aggregates aggregates and forms plaques, that’s why the
• Inhibition of spreading amount of Aβ42 decreases in the CSF. The Tau
and pTau increase since it is normally inside the
Clinical trials neurons, but when these neurons degenerate the
Before the clinical trials, there are studies done level of the CSF increases. Together these
on animal models to see if the drug has toxic proteins are a biomarker for Alzheimer’s disease.
effects.
Phase 1: Studies on effects in healthy Recently researchers measured p-Tau217 in blood
volunteers plasma. In Alzheimer’s disease this protein is
Phase 2: Efficacy and tolerability in a limited increased, but this is not for all diseases.
Treatment for neurodegenerative diseases the effects are mostly temporary, and have a lot
• Symptomatic treatment of side effects.
• Disease modifying
Symptomatic treatment for Parkinson’s disease
Symptomatic treatments A successful treatment is the stimulation of
Affect symptoms but not the cause of the dopaminergic transmission with Levodopa (L-
disease. This includes sleep medication, anti- dopa), which is converted to dopamine within the
depressants, anti-anxiety, and substituting lost brain.
neurotransmitter systems (supply
neurotransmitters to gain the function of
neurons back).
Symptomatic treatment for Alzheimer’s
disease
One of the treatments includes stimulation of
cholinergic transmission. This is based on the Side effects of L-Dopa
fact that in Alzheimer’s disease some of the
cholinergic neurons are lost. This is usually
done by inhibiting an enzyme called
acetylcholinesterase that degrades
acetylcholine in the synaptic cleft, thus
inhibition of this enzyme leaves more
acetylcholine in the synaptic cleft.
Deep brain stimulation
This is a form of non-pharmacological
symptomatic treatment where there is a
Another symptomatic treatment is blocking restoration of neurotransmitters.
the NMDA receptor. This causes inhibition of
glutamate excitotoxicity. This is based on when Stem cell treatment
neurons degenerate they release glutamate. This is also a form of non
pharmacological symptomatic
treatment to restore the
neurotransmission.
Though, after a while, there is a
neuroinflammatory response that works against
the transplantation of these cells, which
contributes to the disease.
Most of the time these treatments are given in
the stages where the disease has already
severely progressed. The treatments are also
limited to a certain group of patients and
, Epidemiological studies showed that the risk number of patients
for Alzheimer’s disease was reduced in people Phase 3: Placebo and/or standard comparator on
that are taking non-steroid anti-inflammatory efficacy and tolerability in a large number of
drugs (NSAIDs, ibuprofen) at high dosages and patients
for a very long time. Phase 4: Continued studies in normal clinical
practice: drug surveillance systems,
Inhibition of the inflammatory response observational studies.
Clinical trial outcome measures are biomarkers
and clinical measures (are the symptoms
Unfortunately, most of the traits with NSAIDs improving?)
showed no evidence for efficacy in Alzheimer’s
disease. The targets of NSAIDs in Alzheimer’s Biomarkers
also affect other cell types such as: • Dopamine transporter PET scan or plaque PET
scan. You can look at this over time, after
treatment, etc.
• Cerebro-spinal fluid (CSF) via a lumbar
puncture. CSF is produced by the choroid plexus
of each ventricle.
CSF diagnosis of Alzheimer’s disease
But why was this included in the
epidemiological studies but not in the clinical
trials? Maybe the positive effects were nog by
anti-inflammatory mechanisms, or they
started it too late and there has already been
an accumulation of Aβ and Tau or it could also
be that it inhibits the good inflammatory
response.
It is based on the levels of Aβ42, Tau, and pTau
Disease-modifying (treatment options) proteins. What is kind of surprising is that Aβ42
• Inhibition of formation of aggregating decreases in the CSF and Tau and phospho Tau
proteins increase. This relates to where these proteins are
• Inhibition of aggregation in the brain. In Alzheimer’s disease Aβ42
• Clearance of aggregates aggregates and forms plaques, that’s why the
• Inhibition of spreading amount of Aβ42 decreases in the CSF. The Tau
and pTau increase since it is normally inside the
Clinical trials neurons, but when these neurons degenerate the
Before the clinical trials, there are studies done level of the CSF increases. Together these
on animal models to see if the drug has toxic proteins are a biomarker for Alzheimer’s disease.
effects.
Phase 1: Studies on effects in healthy Recently researchers measured p-Tau217 in blood
volunteers plasma. In Alzheimer’s disease this protein is
Phase 2: Efficacy and tolerability in a limited increased, but this is not for all diseases.
