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BMSc - Neuropharmacology and Behaviour > Parkinson's Disease > Flashcards

Parkinson's Disease Flashcards

1
Q

What is parkinson’s disease?

A

Progressive neurodegenerative disorder

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2
Q

What are the classical symptoms of PD?

A

Muscle rigidity/ stiffness
Resting rhythmic tremor
Bradykinesia (slowing of physical movement)
Postural instability/ abnormality
Secondary sy; depression, dementia or confusion, speech and swallowing difficulties, drooling, dizziness, impotence, urinary frequency, constipation

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3
Q

What is the basal ganglia?

A

Collection of subcortical nuclei situated within each cerebral hemisphere, and upper brain stem

Includes; 
Caudate
Putamen
Globus pallidus (internal and external) 
Subthalamic nucleus
Substantia nigra; pars compacta and reticulata
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4
Q

What is the role of the basal ganglia within the motor system?

A

Act on the cortex via thalamus
Basal ganglia receives inputs from all cortical areas (not just motor)
Projects to thalamus and then to cortical regions involved in motor planning

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5
Q

Describe basal ganglia connection in a simplified manner

A

Major input to striatum from cerebral cortex

Cortical information is processed in striatum and passed to the internal segment of GP and SNpr

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6
Q

What are the neuropathological hallmarks of PD?

A

Loss of nigrostriatal DA neurons (pars compacta of substantia nigra)
Presence of Lewy bodies (intraneuronal proteinaceous cytoplasmic inclusions)

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7
Q

Describe the substantia nigra (pars compacta) in PD

A

Cell bodies of nigrostriatal DA neurons are in SNpc and project to the putamen (striatum)

SNpc normally contains approx 400,000 nerve cells which contain neuromelanin

Loss of DA neurons results in classical neuro-pathological trait of SNpc depigmentation

Loss of projection to putamen results in DA depletion in putamen

Onset of PD symtpoms; putamental DA depleted 80% and 60% of SNpc DA neurons lost

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8
Q

Describe the neurochemical changes seen in PD

A

Loss of NA neurons of locus coerulous
Loss of 5HT neurons in the midline rahpe nucleus
Loss of ACh neurons in dorsal motor nucleus of vagus
Other regions affected; cerebral cortex, olfactory bulb, ANS, hippocampus

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9
Q

What are lewy bodies?

A

Intracellular structures
Circular, with a dense protein core surrounded by a peripheral halo
Highly filamentous bodies (5-20 nm)
Contains ubiquitin and neurofilament proteins
Alpha-synuclein

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10
Q

What is alpha synuclein?

A

Small hydrophilic protein (140 amino acids) that belongs to a family of related synucleins (beta and gamma)
Natively unfolded protein; has significant structural plasticity
Can aggregate to form insoluble filaments; Lewy bodies

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11
Q

What determines the structural plasticity of alpha synuclein?

A

Dependent on the environment; it can be unfolded, form monomers/ oligomers or amyloidogenic filaments

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12
Q

With what structure in AD are Lewy bodies similar too?

A

Beta amyloid or tau

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13
Q

Is there a genetic component to PD?

A 
Yes; in around 1% of PD patients; there is a pure autosomal trait 
Early onset (<40 yrs)
10 distinct genetic loci associated with PD with mutations in more than 4 genes
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14
Q

What are some of the loci and genes implicated in PD?

A

PARK1; SNCA

PARK2; parkin

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15
Q

Is there a physiological function of alpha synuclein?

A

Highly expressed in mammalian brain - particularly in the presynaptic nerve terminal

a-synuclein -/- mice show that is shows a role in synaptic vesicle recycling and DA neurotransmission

In vitro studies have implicated it in synaptic vesicle recycling as it can bind to acidic phospholipid vesicles

Alpha synuclein plays an important role in regulating synaptic vesicle size and recycling particularly relevant to the storage of nT

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16
Q

What are the key changes seen in alpha synuclein mutant proteins?

A

Self aggregates more readily than WT
Suggests that aggregation of alpha-synuclein is a key event in the pathogenesis of PD
Transgenic mice with mutant alpha synuclein have Lewy body formation and neurodegeneration

Micro expression of A53T mutation develop intraneuronal inclusions, mitochondrial DNA damage and apoptosis of neocortical, brain stem and motor neurons

Over-expression of wt or mutant alpha synuclein in vitro increases ROS production and results in enhanced cell death

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17
Q

Describe lewy body formation

A

Unfolded or disordered alpha synuclein monomers form beta sheet rich oligomers
Protofibrils give rise to more stable amyloid like fibrillar structures
Alpha synuclein fibrils aggregate to form lewy bodies

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18
Q

Describe the role of parkin in PD pathogensis

A

Parkin is an enzyme; E3 ligase. 465 aa protein. E3 ubiquitin ligase
50% of early onset PD is linked to parkin mutations
Parkin mutations result in a loss of function of parkins E3 ligase activity leading to improper targeting of substrates for proteasomes degradation leading to potentially toxic accumulations in neurons

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19
Q

What role do E3 ubiquitin ligases play?

A

Enzyme that tags target proteins with ubiquitin for degradation

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20
Q

Describe the genetic link between ubiquitin and PD

A 
UCH-L1 catalyses hydrolysis of C-terminal ubiquityl esters and is involved in recycling ubiquitin ligated to misfolded proteins 
Dominant mutation (I93M) in UCH-L1 identified in one family with inherited PD

Impaired activity of ubiquitin system is KEY for PD pathogenesis

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21
Q

Describe the link between DJ-1 in PD

A

Highly expressed in the brain
Localised to mitochondria and may be important in mitochondrial function. DJ-1 is thought to be a cellular monitor of oxidative stress

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22
Q

In summary; what are 3 key genes involved in the pathogenesis of PD?

A

Alpha synuclein
DJ-1
Parkin

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23
Q

Describe the ubiquitin-proteasome system

A
  1. Ubiquitin monomers (Ub) are activated by E1 and transferred to Ub-conjugating enzyme (E2)
  2. Proteins are recognized by E3 ligase (parkin) which transfers Ub to a target protein
  3. Ub monomers are attached by lysin residue (K) causing poly Ub conjugation
  4. Poly Ub chains are linked by K29/K48 signal target proteins for degradation into smaller peptide fragments
  5. Poly Ub chains are recyclyed to free monomers by enzymes like UCH-L1.
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24
Q

What is the role of LRRK2 in PD pathogenesis?

A

PARK8 encodes for protein called dardarin
Kinase
One common mutation is G2019S which is a functional mutation which increases kinase activity

Member of MAPK family. In vitro; LRRK2 phosphorylates substrates required for activation of JNK and p38 MAPK

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25
Q

What is moesin?

A

Substrate for mutant LRRK2

Ezrin-radixin-moesin protein family member (stress activated protein kinase family) that regulates neurite outgrowth and the cytoskeleton

In hippocampal neurons; mutant LRRK2 interacts with alpha/beta tubulin, a component of the cytoskeleton

LRRK2 is involved with cytoskeleton motility and vesicular trafficking which may play a role in PD pathogenesis

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26
Q

What are the 2 main hypothesized mechanisms of neurodegeneration in PD?

A

Misfolding and aggregation of proteins leading to death of SNpc DA neurons

Mitochondrial dysfunction and consequently oxidative stress and cell death

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27
Q

What evidence is there for the misfolding and aggregation of proteins?

A

Protein deposition is likely to be toxic to neurons

Inherited PD; pathogenic mutations may directly induce abnormal protein conformations (alpha synuclein), or indirectly interfere with processing of misfolded proteins (parkin, UCHL-1)

Sporadic; direct protein damaging modifications and indirect changes in processing of misfolded proteins have also been detected 
Oxidative dress (ROS) is thought to be a possible trigger for dysfunctional protein metabolism
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28
Q

What is the evidence for mitochondrial dysfunction and oxidative stress?

A

Defects in oxidative phosphorylation in PD suggested as MPTP blocks mitochondrial electron transport chain by inhibiting complex 1 (NADH dehydrogenase)

Abnormalities in mitochondrial complex 1 have been identified in PD

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29
Q

Describe the mitochondrial ETC

A

NADH binds to complex 1 and passes 2 electrons to FMN group
FMN is reduced to FMNH2
Electrons are passed to iron sulphur proteins leading to reduction in Fe2+

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30
Q

What are the effects of complex 1 (ETC chain) inhibition?

A

Inhibition of complex 1 increases ROS superoxide

This forms a toxic hydroxyl radicals or can react with NO to form peroxynitritie

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31
Q

What are the consequences of hydroxyl radical formation or peroxynitrite formation?

A

Cellular damage by reacting with nucleic acid, proteins and lipids

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32
Q

What evidence is there to show that complex 1 inhibition is implicated in the pathogenesis of PD?

A

Biological markers of oxidative damage are elevated in PD

Content of anti-oxidant glutathione is reduced in PD brains

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33
Q

How do cells ultimately die in PD?

A

In programmed cell death (PCD), intracellular signalling pathways are activated that result in cell death

Physiological PCD (apoptosis) is known to be crucial during normal development and as a homeostatic mechanism (e.g. immune system)

Dysregulation can contribute to neurodegeneration

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34
Q

Is there any evidence for PCD in PD?

A

Increase in bax-positive staining in the SNpc DA neurons in PD

Increased neuronal expression of Bax in PD suggesting that cells are undergoing PCD

Other molecular markers are altered in PD including caspase-8, caspase-9 and Bcl-xL

This suggested that PCD machinery is activated in postmortem in PD tissue

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35
Q

What is Bax?

A

PCD molecule

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36
Q

What toxin based models are used in PD?

A

6-OH-DA
Paraquat
Rotenone
MPTP

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37
Q

What gene based models are used in PD?

A

Synuclein

Parkin

38
Q

Describe the 6-OH-DA model in PD

A

1st animal model of PD assoc with SNpc DA cell death

6-OHDA induced toxicity is selective for DAergic neurons (preferential uptake by DA transporter)

In neurons; 6-OHDA accumulates in cytosol, generates ROS and inactivates various molecules by generating quinone that attack nucleophilic groups

Gradual loss of DAergic neurons will be seen after 6-OH-DA - 80% loss after 6 weeks

39
Q

What are the different types of 6-OH-DA models?

A

Dependent on the site of injection into the nigrostriatal pathway:

a) medial forebrain bundle (MFB): leads to excessive DA depletion
b) SNpc: leads to more specific and moderate DA depletions
c) sub regions of caudate-putamen (CPu): leads to specific DA depletions

Rats with partial lesions of the ventrolateral caudate/putamen are more appropriate models to stufy

40
Q

Describe the pros and cons of the 6-OH-DA model for OD

A

Pros:
Good model for assessing anti-PD actions of new drugs as unilateral striatal lesions causes quantifiable (degree of lesion) asymmetric circling behaviour in animals

Cons:
Not clear if mechanism of cell death is similar to human PF.
6-OH-DA induced pathology differs from PD (no lewy body formation)
Pathology varies depending on injection site of OHDA

41
Q

Describe the MPTP neurotoxin based model of PD

A

MPTP found to be neurotoxic contaminant
In humans and monkeys; MPTP produces irreversible and severe PD syndrome; characterized by tremor, ridigit, slowness of movement, postural instability and freezing

Most studies of MPTP performed in monkeys and rodents as only 4 human MPTP cases have come to autopsy

42
Q

Describe the similarities and differences of MPTP to PD

A

Similarities; low dose MPTP treated monkeys show preferential degeneration of the striatum DA nerve terminals. Regional pattern of MPTP-induced damage is similar to PD (> cell loss in SNpc than VTA; DA neuromelanin-containing cells are more susceptible to damage)

Differences;
Other monoaminergic neurons (locus coeruleus) are not damaged by MPTP
Classical lewy bodies are not found in MPTP humans/ monkeys

43
Q

What is the benefits of a MPTP based model?

A

Monkey MPTP model is used to assess novel treatments for PD symptoms
For example; EP studies reveal hyperactivity of STN as a key factor in PD motor dysfunction: this lead to targeting of STN in DBS procedures to reduce motor function in PD patients

Mouse MPTP; enhanced out understanding of mechanisms of DA neurodegeneration

44
Q

Describe MPTP metabolism

A
  1. After systemic administration, MPTP crosses BBB
  2. In brain: MPTP is converted to MPDP+ by MAO-B in non-DA cells, then into MPP+ by unknown mechanisms
  3. MPP+ released into extracellular space and concentrated into DA neurons via DAT
45
Q

What happens to MPP+ once inside DA neurons?

A
  1. Concentrate in the mitochondria where is blocks complex 1. This results in enhanced ROS production and reduces ATP synthesis (toxic)
  2. Interacts with cytosolic enzymes (toxic)
  3. Sequesters into synaptic vesicles via vesicular monoamine transporter (VGAT)
46
Q

Describe the paraquat (pesticide) based model for PD

A

Herbicide that induces a toxin-model of PD
Similar structure to MPP+
Exposure to paraquat increases risk of PD
Does not easily cross BBB; instead, toxicity is due to superoxide radial formation
Systemic administration in mice leads to SNpc neuro-degeneration and alpha synuclein containing inclusions

47
Q

Describe the pros and cons of paraquat PD models

A

Pros:
Useful to study role of alpha-synuclein in neurodegeneration (reliably causes DA cell loss and alpha synuclein positive inclusions)

Cons:
Not known if DA toxicity is selective or other neurons are affected

48
Q

What is the difference between paraquat and MPP+?

A

Paraquat has an N-methyl-pyridinium group whereas MPP+ has a phenyl group

49
Q

Describe the use of rotenone as a model for PD

A

Member of rotenoid family of cytotoxic compounds

Insecticide and fish poison

Highly lipophilic; gains access to most organs

Binds to the same site as MPP+ on the mitochondria to inhibit complex 1 of ETC

IV rotenone in rats; selective degeneration of DA neurons and alpha synuclein positive inclusions

Rotenone-treated rodents develop abnormal posture and slowness of movement

50
Q

Describe the pros and cons of rotenone as a PD model

A

Pros:
Good model for studying relationship between aggregate formation and cell death

Cons:
Rotenone has widespread neurotoxic actions; not DA selective

51
Q

Describe the theory of genetic models in PD

A

Discovery of PD genes has allowed the generation of specific genetic models with specific significance to PD
Expectation is that genetic and sporadic forms of PD share similar pathogenic mechanisms
Studies in genetic models focus research on key biochemical pathways

All PD genes (alpha synuclein, parkin, UHCL-L1) influence ubiquitin protein, degradation of proteins or influence on mitochondrial function

52
Q

Describe the alpha synuclein model of PD

A

Mice overexpress normal or mutated alpha synuclein

Severity of phenotypes depends on promotor used to make transgene

Overexpression of alpha synuclein in WT; neurochemical deficits in nigrostriatal pathway, behavioural abnormalities, alpha synuclein accumulation

Mice also show accelerated age related loss in neurons

53
Q

Describe the parkin mouse model in PD

A

Loss of function of parkin (E3 ligase); most are recessive. Most models focus on parkin -/- mice

54
Q

Describe a quaking mouse mutant (parkin PD model)

A

Spontaneous deletion of parkin. Mice have myelin deficiency and enhanced DA metabolism

Mice display behavioural deficits and tremor in the trunk region and extremities

55
Q

Describe the parkin k/o mouse (defective exon 3) in the parkin PD mouse model

A

Mice have progressive motor anomalies and deficits in sensorimotor integration

Paradoxically, mice have an increased basal release of DA and reduced striatal neuronal excitability

56
Q

Summarize the genetic mouse models in PD

A

Both alpha synuclein overexpress mice and parkin -/- mice do not reproduce the full spectrum of anomalies found in humans. In particular, specific loss of nigrostriatal DA neurons

The models however show clear sensorimotor anomalies

Parkin -/- mice show reduced levels of proteins involved in mitochondrial function and oxidative stress

Models offer the chance to elucidate ea`rly changed caused by parkin mutations that lead to neurodegeneration

57
Q

Where is large DA found?

A

Corpus striatum
Limbic system
Hypothalamus

58
Q

How is DA synthesized?

A

Catecholamine Synthesis:
Tyrosine to dopa via tyrosine hydroxylase activity followed by decarboxylation to form DA

DA can then be further broken down to adrenaline and NA by dopamine beta hydroxylase

59
Q

How is DA uptaken and metabolised?

A

DA taken up by a specific DA transporter
Metabolised by MAO-B and COMT to form:
DOPAC
HVA

60
Q

What are the different dopamine receptors?

A 
D1 class (D1 and D5): stimulated adenylyl cyclase and cAMP
D2 class (D2,3,4): inhibit adenylyl cyclase; reduce cAMP
61
Q

Where are DR receptors distributed?

A

D1,5; brain and smooth muscle. Mostly post-synaptic inhibition
D2,3,4; brain, CV, presynaptic nerve terminals. Pre and post synaptic inhibition

Only D2 and D3 are expressed presynaptically
Regulation of DA release is modulated principally by D3 autoreceptors
Regulation of DA biosynthesis and metabolism is mediated by D2

62
Q

Describe the DA pathways within the brain

A

Nigrostriatal; motor control (SNpc (midbrain) to corpus striatum)
Mesolimbic cortical: emotion and reward (VTA (midbrain) to limbic system, cerebral cortex and striatum)
Tuberohypophysial: endocrine control (Arcuate nucleus of periventricular area (hypothalamus) to infundibulum, anterior pituitary)

63
Q

How is motor processed in the BG?

A

Balance between direct (nigral-striatal) and indirect (striatal-pallidal)

Inhibitory influence of direct pathway on BG output (SNr/ GPi) is counterbalanced by the disinhibitory influence of the indirect pathway

64
Q

Describe the receptors involved within the direct pathway of BG

A

Dynorphin containing medium spiny neurons

DA acts at D1 receptors to excite dynorphin containing medium spiny neurons

65
Q

Describe the receptors involved with the indirect pathway of BG

A

In striatum, DA acts on postsynaptic D2 receptors expressed on enkephalin containing striatal pallidal neurons, resulting in their inhibition

66
Q

What goes wrong in PD at the BG level?

A

Lack of DA causes reduced activation of striatal D1 and D2 receptors.
This results in :
Reduce inhibition in indirect pathway
Decreased excitation in direct pathway

Net result: excessive activation of GPi-SNr complex and over inhibition of thalamocortical centres

67
Q

What are the current pharmacological therapies to treat PD?

A 
Increase production of endogenous DA
Drugs that mimic DA action 
Drugs that prevent degradation of endogenous (MAOB) or exogenous DA (COMT) 
Drugs that release dopamine 
Muscarinic cholinergic antagonists
68
Q

Describe levodopa

A

1st line: DA precursor that crosses BBB
Combined with dopa decarboxylase inhibitor (e.g. carbidopa) to reduce dose required and reduce peripheral side effects

In periphery; decarboxylase inhibitor prevents levodopa conversion to DA

In brain: decarboxylase Is do not penetrate BBB and decarboxylation occurs rapidly

69
Q

Describe the kinetic aspects of levodopa

A

Well absorbed by small intestine via active transport
At start of treatment; 80% patients show improved function with 20% showing complete cure
BUT effectiveness of levodopa gradually declines
This is due to:
Natural progression of disease
Receptor downregulation

70
Q

What are some acute side effects of levodopa

A

Nausea and anorexia
Hypotension
Psychological: hallucinations, delusions (schizophrenic like symptoms due to increased DA within mesolimbic pathway)

Slowly developing as PD progresses: dyskinesia, on/off effect

71
Q

How can the long term side effects of levodopa be counteracted?

A

Animal models and clinical studies indicate more effective control with a continuous supply of DA
E.g. MPTP treated primates show reduced motor complications if treatment involved a long acting DA agonist rather than short acting
Continuous infusion devices however are very impractical for PD patients

72
Q

Describe the action of selegiline (MAO-B Inhibitor)

A

MAO inhibitor - selective for MAO-B which predominates in DA containing regions
DA levels are increased as metabolism of DA is blocked
Lacks unwanted peripheral SE of non-selective MAO Is
MAO-B inhibition protects DA from intraneuronal degradation

73
Q

Describe DA receptor agonists

A

Selective D2 agonists produce consistent anti-parkinsonism effects whereas D1 receptors may produce a broader rage of effects

Bromocriptine (potent D2R); longer duration of action (half life is 6-8hrs)
Apomorphine (s/c via continuous pump)
Lisuride
Pergolide (D1/2 agonist)

SE: similar to levodopa; limits doses that can be used

74
Q

Describe the role of muscarinic antagonists in PD

A

Normally, the cholinergic system in the striatum is restrained by the DAergic pathway
Antagonise the action of ACh to limit this activity to makeup for a lack of DA

75
Q

Describe the role for adenosine A2A receptor antagonists in PD

A

Adenosine A2A receptors have a very restricted expression in the CNS; enriched in the striatum
High levels are expressed on D2 receptors (enkephalin) expressing GABAergic striatal neurons
Studies have shown functional interactions between A2A and D2 receptors
E.g. activation of A2ARs opposes the effects of D2rs by decreasing the affinity for DA D2Rs activating signalling cascades that D2Rs inhibit

Consequently, A2AR antagonists would be expected to enhance effects of DA on striatal neurons

Blocking A2ARs should partially reinstate the thalamocortical motor stimulatory activity

76
Q

Why is the use of mAChR limited?

A

Thy reduce tremor more than rigidity/ hypokinesia

Troublesome SE; dry mouth, constipation, impaired vision, urinary retention

Mainly used for parkinsonism induced by antipsychotics

77
Q

Is there any experimental evidence for anti-parkinsonian action of A2ARs?

A

A2AR antagonists increase basal locomotion in rats

In a hypoDAergic rodent model of motor function induced by haloperidol; A2AR antagonist reverses haloperidol induced catalepsy

A2AR blockage improves abnormal muscle tone and tremor in PD models

A2A antagonists completely reverses tremulous jaw movements and haloperidol induced catalepsy

78
Q

What are the neuroprotective actions of A2A antagonists?

A

Coffee/ tea drinking (caffeine intake): assoc with reduced risk of PD in humans (caffeine = AR antagonist)

In rodent models; caffeine and other selective A2A antagonists protect against DA neuronal toxicity

Mice given caffeine display dose-dependent reversal of MPTP induced loss of nigrostriatal DAergic neuros

79
Q

What are the side effects of A2AR antagonists?

A

Pro-inflammatory
Ischaemic tissue damage (cardiac, renal, hepatic)
Psychosis
Insomnia

80
Q

Describe the role of neural transplantation in PD

A

As PD results from the selective loss of SNpc DA neurons

Injection of dissociated foetal cells into the SNc

81
Q

What are the pros and cons of stem cells for neural transplantation in PD?

A

Very promising
Stem cells can be induced to become DA neurons and in theory could completely replace DA neuron loss

Cons; tumour formation, tissue rejection

82
Q

Can stem cells be used or neural transplantation in place of foetal tissue?

A

Embryonic stem cells (ESC); can differentiate into neurons

Induce pluripotent stem cells (iPSC); adult stem cells that can differentiate into DA neurons specifically

83
Q

Describe the role of deep brain stimulation in PD

A

Increasingly accepted as an adjunct therapy for PD
Surgical treatment; intractable tremor, long term complications of L-dopa

Subthalamic nucleus and GPi are targeted; with studies to show that STN stimulation is superior to GPi as it produces a more pronounced anti-akinetic response

84
Q

Describe how STN stimulation works to mitigate PD symptoms

A

STN controls the output nuclei of the basal ganglia (GPi, SNr)
STN recieves input from GPe and cortex, perifascicular nucleus of thalamus and PPN

85
Q

Are there any other surgical procedures utilised in PD?

A

Lesioning; thalamotomy, pallidotomy, subthalamotory

Pallidotomy is more common type and targets the GPi leading to relief of: 
Tremor
Rigidity 
Bradykinesia
Motor fluctuations 
Dyskinesia
86
Q

Has gene therapy been utilised in PD?

A

Less than invasive; may halt progression of PD
Technique uses viral vectors to introduce a protein of interest (neuroprotective or neurorestorative) into a specific brain region

87
Q

How do viral vectors reach the brain?

A

Port into the subthalamic nuclei. The virus delivers a gene that prompts the cell to produce GAD
GAD (glutamate decarboxylase) is the key enzyme that synthesizes GABA

88
Q

Why is GAD the gene therapy of choice in PD?

A

Forms GABA

In PD: STN is disinhibited resulting in pathological excitation of its targets (GPi and SNpr)

In turn; increased GPi/ SNpr outflow is though to underlie tremor, rigidity and bradykinesia

Therefore, increased GABA in STN will alleviate this by inhibiting STN activity

89
Q

Is there evidence that GAD gene therapy works?

A

PD patients are currently taking part in clinical trials o deliver GAD to STN; currently no serious adverse effects but only a small no. patients have been studies

90
Q

What is another protein (not GAD) targeted in PD gene therapy?

A

GDNF; growth factor that promotes DA survival and regeneration in rodent and primate PD models

Several methods of GDNF delivery have proven to prevent the loss of DA neurons in animal models of PD

Human cases; success is variable.

91
Q

What are the potential problems with gene therapy?

A

Short term results; patients must undergo treatment every few months

Immunological; immune system can identify and destroy the viral vector

Toxicity; viral vector may mutate and become pathogenic

BMSc - Neuropharmacology and Behaviour (27 decks)

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