Therapy of Genetic Disorders
○ Lactose restriction for Lactase deficiency; phenylalanine restriction
○ Vitamin C for Scurvy, Biotin for Biotinidase deficiency, Starch for G-
Chelation and enhanced excretion
○ copper chelation for Wilson Disease
○ allopurinol for gout, Statins for hypercholesterolemia
Somatic Gene Therapy
Introduction of recombinant genes into somatic cells
to treat genetic or acquired disease
• applicable to any disease with molecular basis of
• currently does not involve removal, repair or site-specific
replacement of mutant genes
• need repetitive therapy
• All gene therapy so far in people has been directed at somatic
In the 1980s, Scientists began to look into gene
They inserted human genes into a bacteria cell.
Then the bacteria cell would transcribe and translate the
information into a protein
Then they would introduce the protein into human cells
The First Case
The first gene therapy was performed on
September 14th, 1990
Ashanti DeSilva was treated for SCID
○ Sever combined immunodeficiency
Doctors removed her WBC
○ inserted the missing gene into the WBC, then
○ put them back into her blood stream.
This strengthened her immune system
worked for a few months
Real treatments performed with
Severe Combined Immunodoficiency (SCID)
Mutation on Chromosome 20 is often to blame
How It Works
Real treatments performed with
• not cure of the disease
• maintenance of venous access to administer the therapy
• requirement of frequent, repeated administrations
• allergic, inflammatory and immune responses to the
• • …
..Adult Stem Cells
•Stem cell collected from adult
can be harvested from many area
including the bone marrow.
•Alternative to Embryonic Stem
•Potential to reverse and cure
..Embryonic Stem Cells
•Use undifferentiated cell from
embryos and cultures them to
grow into need cells
•Neurons Grown from Embryonic
Stem Cells Restore Function in
•Hold potential cures for 1000s of
diseases many genetic disorders.
•Many ethical and social concerns
surrounding this research
•Using stem cells to replace
or create tissues and organs
•Currently heart tissues and
full bladders are being grow
Fig. Stem cell treatments and
tissues recreated in the heart
of a child
Advanced IVF Techniques
•This treatment is aimed at
women who would pass on a
genetic defect to the child.
•Also helps women who suffer
with mitochondria disease.
•Faulty genes are removed from
the embryo, and replaced by
healthy genes from the additional
Who decides what
diseases to cure?
Who will have
access to therapy?
Is it interfering with
Is it alright to use
the therapy in the
prenatal stage of
Courtesy of www.cbs.dtu.dk
all Inherited and acquired
The Bubble Boy
In 2002, then 18-month-old
Rhys Evans received
one of the first
successful gene therapy
treatments for a genetic
disorder, which cured
his severe combined
Courtesy of news.bbc.co.uk
2002- Scientists are able cure children of SCID.
2003- Researchers are able to insert genes to
the brain, opening up a wider variety of
diseases that could be cured.
2006- Successfully treat two cancer patients.
Gene therapy could be
very different for different diseases
• Gene transplantation
(to patient with gene deletion)
• Gene correction
(To revert specific mutation in the gene of interest)
• Gene augmentation
(to enhance expression of gene of interest)
• Change the regulation of gene repairs
From: Alberts et al. Molecular Biology of the Cell
The Gene Therapy
1. A desired gene is selected and
inserted into a genome to replace an
“abnormal”, disease-causing gene.
2. The genome is then transferred into
a vector, most commonly an
adenovirus, which will transport the
gene into the patient.
3. The vector is sent to a target cell in
the patient’s genome and then
“unloads” the genetic material in the
4. Once the genetic material has been
inserted into the target cell, the cell
will continue its reproductive cycle
with the new therapeutic gene . This
will cause new generations of cells
with the integral therapeutic gene
which will cure the desired disease in
Non viral vectors
Un complexed plasmid DNA
DNA coated gold particles
DNA – protein conjugates
Problems with Gene
Difficult to integrate desired DNA into a genome.
Effects are usually temporary
Immune system automatically attacks foreign objects reduce
effects of gene therapy.
The possibility of the modified adenovirus to revert back to its
In rare cases therapy has induced tumors leukemia (if
integrated in a tumor suppressor gene because insertional mutagenesis)
Heart disease, Hypertension, Alzheimer’s, arthritis, diabetes : hard to treat
Until today : Efficacy in any gene therapy protocol not definitive.
Problems with Gene
Funding for therapy fluctuates with
rise and fall of success.
Most funding in government
research, + $400 million a year.
Difficult to afford and can’t be
covered by insurance.
Economic market : something new?
Courtesy of dir.nichd.nih.gov
FDA hasn’t approved any human gene therapy product
18-year-old Jesse Gelsinger died from multiple organ
failure 4 days after treatment
Death was triggered by severe immune response to adenovirus carrier
January 2003, halt to using retrovirus vectors in blood
stem cells because children developed leukemia-like
condition after successful treatment for X-linked SCID
Inadequate understanding of biological interactions of
vector and host.
The Future treatment for genetic disorders is
Experimental (incld. Gene Therapy)
It is not currently available outside a clinical trials