TERAPI PENYAKIT GENETIKA

DAN
PERKEMBANGAN TERKINI
 TERAPI PENYAKIT GENETIKA TERKINI R

1. Terapi Preventif
2. Manipulasi Metabolik
3. Gene Product Replacement
4. Transplantasi sel dan organ
5. Gene Therapy
1. Terapi Preventif
• Diagnosis prenatal
• Diagnosis Preimplantasi
(in vitro fertilization, testing of embryo & implantation of normal
embryo)
• Skrining pencegahan onset penyakit.
2. Manipulasi Metabolik
 Pembatasan Diet makanan
Contoh : - Pembatasan diet Laktosa pada defisiensi enzim laktase
- Pembatasan phenylalanine pada penyakit phenylketonuria
 Pemberian suplemen
Contoh : - Pemberian Vitamin C pada Scurvy
- Pemberian Biotin pada defisiensi Biotinidase
- Starch pada defisiensi G-6-P
 Chelating agent dan meningkat ekskresi
• copper chelation pada Wilson Disease
 Inhibitor metabolik
• Pemberian allopurinol pada gout
• Pemberian statin pada hiperkolesterolemia
3. Terapi Produk Gen
Terapi penggantian hormon, protein atau enzim
• Suplementasi hormon:
o Hypothyroidism: hormone thyroid
o Congenital adrenal hyperplasia: hormon cortisol
o Growth hormone
• Hemophilia : menggunakan protein faktor pembekuan
• Diabetes: hormone insulin
• Penggantian enzim
o Beta glucosidase : penyakit Gauchers
o Alpha glucosidase: penyakit Pompe
o Adenosine deaminase (PEG): ADA- SCID
4. Transplantasi sel atau organ
• Transplantasi sel :
• Transplantasi sumsum tulang (bone marrow) pada penyakit imunodefisiensi
• Tranplantasi organ :
• Transplantasi ginjal pada penyakit Fabry disease
• Transplantasi liver pada Tyrosinemia
5. Gene Therapy
 Gene therapy is a treatment or cure for disorders caused by mutated
genes.
 It involves adding a normally functioning copy of the gene(s) to enough
affected cells to restore normal function.
 Introduction of normal gene
• Somatic
• Germ line
 Therapy of noninherited disorders
• (cancer, AIDS)
 Production of gene product for administration
• (hemophilia, growth hormone, erythropoietin)
Somatic Gene Therapy
Introduction of recombinant genes into somatic cells to treat genetic or
acquired disease
• Does not involve germ line
• Applicable to any disease with known molecular basis of pathogenesis
• Currently does not involve removal, repair or site-specific replacement
of mutant genes
• May not require permanent alteration of cells (repetitive therapy)
Disease Characteristics Currently Ideal for Gene
Therapy
• Lethal disorder
• Course not highly variable
• Reversible
• No universal therapy
• Gene cloned
• No tissue specificity or regulation
• Bone marrow cells involved
Somatic Mosaicism:
Reversion of an Inherited Mutation to Normal and Selective
Growth Advantage
Mutant

Reversion of mutation
to normal

Mutant cells Normal cells

“Successful” Gene Therapy for Immunodeficiency
Diseases: 2005
• Retroviral vector used despite major disadvantages

• Over 14 patients with X linked severe combined immunodeficiency of 3

different types have been treated successfully

• Oncogenic insertion in two of 14 children-leukemia

• - X-linked SCID trials suspended but now reinstituted

• ~8 patients with ADA deficiency treated

Gene Therapy Successes
• Although no gene therapies have been approved by the FDA for sale, some
diseases have been experimentally successful:
• Melanoma (skin cancer)
• Severe Combined Immunodeficiencies
• Hereditary Blindness
• Sickle Cell Anemia
How is it done?
Viral Vector Carrying Healthy Gene

Cell with mutated Vector inserts New gene in the

gene(s) healthy gene into cell along with
cell original genes
Functional proteins are created from the therapeutic gene
causing the cell to return to a state.
Gene Therapy
To design and carry out a gene therapy treatment, a researcher must:
1.Identify the gene(s) responsible for the disorder.
2.Make copies of the normal gene.
3.Insert the copies into vectors.
4.“Infect” the affected cells with the vectors.
5.Activate the gene so that transcription and translation take place.
Gene Therapy Disappointments
• In 1999 a boy died due to an immune response to an adenovirus gene
therapy vector.
• Four children have developed cancer due to a retrovirus gene therapy
vector
TERIMA KASIH
SELAMAT BELAJAR
SEMOGA SUKSES!!