PD - Potential Therapies Flashcards
Give examples of potential therapies for PD
Adenosine A2A receptor antagonists Neural Transplant Stem cell transplant Deep brain stimulation and surgery Gene therapy
Where are adenosine A2A receptors found?
Striatum
How does A2A oppose D2 effects?
Decreases DA affinity for D2
Activates signalling cascades which are normally inhibited by d2
Why may adenosine A2A receptor antagonists be useful in PD?
Block the effects which are in opposition of D2
To reinstate thalamocrtoical motor stimulatory activity
Give an example of an A2A receptor antagonist
SCH58261
KW-6002
KF17837
What findings from rat models support the idea of adenosine A2A receptor antagonists as suitable therapy?
SCH58261 - increased basal locomotion
KW-6002 reversed haloperidol induced akinesia
KF17837 improved jaw movemetns, muscle tone and tremor in PD models
Which natural adenosine A2A receptor antagonist has been studied?
Caffeine
What is the effect of caffeine in PD rodent models?
Protects against DA toxicity in rodents and reverses MPTP-induced loss of DA neurons
What are the systemic effects of adenosine A2A receptor antagonists?
Inflammation, ischaemic
What are the CNS effects of adenosine A2A receptor antagonists?
Psychosis
Insomnia
Explain the concept of neural transplant to treat PD
Replace the lsot DA neurons but injection of foetal midbrain neurons to the substantia nigra pars compacta
What are the clinical findings of foetal neuron transplants?
Maintain function and improve symptoms for up to 15 years
Why are neural transplants not used more commonly?
Ethics
Not a renewable solve
Compare animal model findings to human findings of neural transplant
More success in animal models
Variable success in actual patients
Explain the concept of stem cell transplant to treat PD
Get embryonic stem cells and induce them to replicate into DA neurons
Theoretically this should replace lost neurons
What is the downside to stem cell transplant
May lead to tumour formation or tissue rejection
What is deep brain stimulation?
Use of a stereotactic frame to insert a needle to the target area - normally the STN
Stimulator box inserted into the subclavicular space
What is deep brain stimulation generally used for?
Adjunct therapy for intractable tremor or long term levodopa
What are the advantages of deep brain stimulation?
Better control
Longer relief time than medications
Reduced dose of meds needed
Relief from pain and insomnia
What are the acute disadv of deep brain stimulation?
Tingling
Speech problems
Dizziness and balance
What are the chronic disadv of deep brain stimulation?
Loss of strength
Depression
Also side note the electode could break like in ur head
What is the most common surgery performed in PD?
Pallidotomy
Which symptoms does a pallidotomy improve
Tremor
Rigidity
Bradykinesia
Which structure is removed in a pallidotomy?
The globus pallidus interna
Explain the concept of gene therapy as a treatment for PD
Use viral vectors to introduce a protein to specific brain region which increases GABA levels
The increased GABA then inhibits the effects of a BG output
Such as tremor, ridigity and bradykinesia
Why gene therapy over surgery?
Less invasive
What are the main side effects of gene therapy?
No serious side effects
But only small studies done so far!
How does GDNF delivery help PD?
Prevents DA neuron loss in neurotoxin exposure
