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Parkinson Day 23 Edit Background
Parkinson Day 23 Edit Background
Out line
Epidemilogi
Treatment saat ini
Future treatment
Pembedahan
"Moving in Harmony with Movement Disorders"
Introduction
PD is the 2nd most common
neurodegenerative disease after
Alzheimer’s disease with
prevalence of 0.5-1% among
those 65-69 y.o, rising to 1-3%
among person ≥80 y.o
Projected growth rates in number of individuals > 50 with Parkinson disease in
the most populous nations in the world from 2005 - 2030.
"Moving in Harmony with Movement Disorders"
40–49 years to 1,903 per South America 228 637 2,180 6,095
100,000 people in individuals
≥801 Europe/
North America/ 113 540 1,602 2,953
• Comparing regions of the world, Australia
1999–2002:1 Uncompensated
19.9%
Outpatient
• Direct costs: $10,349 per patient care care
7.5%
• Indirect costs: $25,326 per patient 18.8%
Years
Dyskinesia, Postural
Patient Symptoms Signs of levodopa “On-Off” Instability,
“wearing-off” Motor Freezing, Falls,
Fluctuations Dementia
Only a small
percentage of oral
levodopa reaches
the brain1 Acceptable
tolerability
profile5
Early wearing-off
leading to reduced
quality of life2,3
Improvements in
quality of life seen
Motor fluctuations in short term6
and dyskinesia will
develop over long
term treatment3,4
1. Nutt & Fellman. Clin Neuropharmacol 1984;7(1):35–49; 2. Chapuis et al. Mov Disord 2005;20:224–230;
3. Freitas et al. Semin Neurol 2017;37(2):147–157; 4. Hametner et al. J Neurol 2010;257(Suppl 2):S268–S275;
5. Ferreira et al. Eur J Neurol 2013;20(1):5–15; 6. Sethi. Neurologist 2010;16(2):76–83
"Moving in Harmony with Movement Disorders"
1. Wolters & Baumann. Parkinson Disease and Other Movement Disorders. 2014;
2. Jenner. Transl Neurodegener 2015;4:3;
3. Chaudhuri et al. Parkinsonism Relat Disord 2016;33(Suppl 1):S2–S8
"Moving in Harmony with Movement Disorders"
"Moving in Harmony with Movement Disorders"
Properti farmakologis
Golongan alkaloid aporphine, formula: C17H17NO2, bersifat lipofilik, afinitas terhadap reseptor dopamine
spektrum luas : D1 dan D2-like receptor (D1, D2S, D2L, D3, D4, D5), sementara agonis dopamine seperti
pramipexole dan ropinirole hanya pada D2 dan D3, serta memiliki pula moieitas piperidine.
Bioavailabilitas oral sangat terbatas (<4%), karena metabolism hepatik tingkat 1 hampir komplit.
Saat ini yang telah berlisensi: sediaan parenteral injeksi subkutan atau infus, bioavailabilitas 100%, distribusi
volume, waktu paruh dan klirens plasma antara kedua sediaan berimbang.
Faktor yang mepengaruhi injeksi subkutan: lokasi injeksi, kondisi kulit, volume dan kedalaman injeksi, dan
adanya nodul subkutan.
Konsentrasi puncak pada darah (Cmax) 10 menit, konsentrasi maksimal dalam LCS setelah 30 menit, waktu
paruh sekitar 33 menit, onset respons klinis umumnya dalam 7-10 menit.
"Moving in Harmony with Movement Disorders"
"Moving in Harmony with Movement Disorders"
Apomoíphine Pump
• Improve QOL
AE, adverse event; LEDD, L-dopa equivalent daily dose; QOL, quality of life.
a. Katzenschlager R, et al. Lancet Neurol. 2018;17:749-759; b. Drapier S, et al. J Neurol. 2016;263:1111-9.
"Moving in Harmony with Movement Disorders"
Efikasi
Hasil berbagai studi open label : memperbaiki kondisi sudden “off” pada PP
stadium lanjut walaupun terapi oral optimal.
Penurunan waktu “off”
Penurunan keparahan dyskinesia (hasil masih inkonsisten)
Studi perbandingan apomorphine dan levodopa → skala efek yang ekuivalen
Perbandingan efikasi apomorphine dan levodopa:
LEVODOPA
INTESTINAL GEL
"Moving in Harmony with Movement Disorders"
"Moving in Harmony with Movement Disorders"
Gene therapy
• There are many potential risks of gene
therapy:1
Gene therapy is the use of genetic material (DNA or RNA) as an o Uncontrolled overproduction of the
agent to alter cellular/biological function and treat disease – targeted protein, resulting in adverse
either to correct a genetic flaw or to introduce new genes1 effects
This can be done in two different ways:1 o ‘Insertional mutagenesis’, where the
Ex vivo – where the manipulation is performed outside of introduced gene inserts into the host
the body, in cell culture genome at a site promoting cancer
In vivo – where the manipulation is performed within the o Induction of an autoimmune and
body inflammatory response
There are many potential candidates for gene therapy, including • The serious risk of insertional mutagenesis can
the LRRK2 gene, the Parkin gene and the SCNA gene1 be controlled by the use of ex vivo methods,
and the careful selection of the method of
insertion within the genome1
1. Zhu et al. Int J Neurosci 2016;126(11):955–962; 2. Barker et al. Nat Rev Neurol 2015;11(9):492–503
"Moving in Harmony with Movement Disorders"
1. Prizer & Browner. J Parkinsons Dis 2012;2(2):79–86; 2. NICE guideline CG35, 2006
"Moving in Harmony with Movement Disorders"
Electrode
Plane of section
Lead Lead
Pulse generator
Electrode Electrode
Globus Subthalamic
pallidus nucleus
“ON” Time
Without
Dyskinesias
Improves from
27% to 74% of a
Patient’s Waking
19%
Day 27%
7%
49%
74%
23%