1. Ha, Stephanie
SPEECH1 – Avila
July 01, 2008
INTRODUCTION
I. Aging is inevitable.
II. We all age as times progresses.
A. For victims of accelerated aging diseases, they age faster than the average human
being…
III. As many may not know, I want to become a biomedical engineer to become indirectly
involved in the medical field to improve humanity.
IV. So, today I am going to talk about a recent and incurable accelerated aging disease:
Hutchingson-Gilford Progeria Syndrome (HGPS)
B. Also known as Progeria.
SPECIFIC PURPOSE: To inform the audience about Hutchinson-Gilford Progeria Syndrome
THESIS STATEMENT: Topic breakdowns for HGPS can be broken down into five segments:
historical background, what is HGPS, why HGPS occurs, symptoms, and treatment.
Transition: Knowing this, let’s proceed to the history of HGPS.
BODY
I. Historical Background (Sarkar, Polleck)
A. First reported in 1886 by Hutchinson and Guilford about a 3.5 year old boy who
possessed the features of an elderly individual
1. Gilford coined the term “progeria” from Greek word, “geras” in 1904
a. “Geras” means old age
B. DeBusk gathers world literature on progeria in 1972
1. Studies four patients
a. Concludes that children die between 7-27
b. Die of cardio or cerebral vascular disease
C. In 2003, the National Human Genome Institute discovered the HGPS gene (Polleck).
1. Known as Lamin A (Kieran, Gordon, etc)
a. Causes progeria
i. Lamins are proteins that contribute to the structure of the
nuclear membrane
• Functions to:
(i) Regulate chromatin
(ii) Maintain nuclear shape
(iii) Maintain nuclear integrity
ii. It is not caused by defective DNA repair but rather, the genetic
mutation of Lamin A (LMNA)
• In other words, a good gene is replaced with a bad one
Transition: Now that we have a history of the disease, let’s move onto what HGPS is.
II. What is HGPS?
A. Rare illness that occurs during childhood
1. From the sources that I’ve gathered, there are about 1 in 4 million to 1 in 8
million occurrences
a. Due to this rarity, it is difficult to determine when a cure will come
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2. 2. However, it is not hereditary.
a. If both parents do not have it, a child, rarely, will attain it.
Transition: After learning what is HGPS, let’s look at why HGPS occurs.
III. Why HGPS Occurs
A. As stated in the previous section, progeria is caused by a genetic mutation in Lamin A
(Refer to Kieran838/Sylvious, continue with product analogy throughout)
1. A refers to a normal DNA sequence of a Lamin A cell, while B refers to a
Progeria one
a. As emphasized earlier, a good gene is replaced with a bad one.
i. In our case, the C is replaced with a T.
2. Think of this genetic mutation as a defective product
a. C is the good part, while T is the defect
3. There are 12 exons (sites) in the lamin gene
a. In Progeria, a joining of Lamin A and a shorter Lamin C in exon 10
results in the formation of some normal and defective Lamin A (hand
/image)
i. Results in removal of 150 nucleotide stretch of exon 11
(hand/image)
ii. Lamin A no longer embedded in membrane (“progerin”)
4. Compare and contrast normal LMNA processing with Progeria (C, image)
5. Explain Fig. 3
Transition: After that, we can go over the symptoms of the disease.
IV. Symptoms (Refer to Kieran, 836 image)  typically don’t appear until 12 months
A. Stunted growth
1. 3-3.5 feet in total height
2. Growth stops at 12 months
B. Loss of hair
1. Bald
2. Thinning
C. Loss of body fat
1. Fragile body
D. Horse-riding stance
1. Stiff joints, angle
a. > 125 degrees
E. As the child ages, his or her features become similar to that of elders.
1. Refers to image
F. Besides these characteristics of the disease, there are associated health risks (Gordon).
1. On average, most deaths are caused by stroke
a. Average age: 13 years
2. Besides stroke, other health risks include:
a. Myocardial ischemia
i. blood deficiency in the myocardium caused by a constriction or
obstruction of blood vessels
b. Infraction (fracture)
c. Acroosteolysis
i. Disease that results in bone loss
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3. • Cold sensation
d. Osteoporosis
e. Arthritis
Transition: After learning about the symptoms, let’s move onto treatment.
V. Treatment (Kieran)
A. Patients should have progeria as the defined disease
B. Patients should have a target to direct therapy
1. Farnesylation is target
2. FTI – farnesyltranferable inhibitor as therapy
a. Also used in cancer treatment
C. Use various established models to target defect
1. Improve phenotype
D. Proposed therapy should keep a record of toxicity files
1. Dependent on severity of disease
E. Trial must have a measure to evaluate the effectiveness of treatment
1. Determines side effects of treatment
F. Eligibility Requirements
1. Patients with HGPS
a. Similar LMNA mutations
2. At least 1 year of weight measurements
a. Demonstrate stable slope
3. Health
a. Should not have a severely impaired liver
i. Or Kidney
b. Tolerance of drugs
i. Should not have gastronomical or
ii. Bone marrow malfunctions
CONCLUSION
I. Therefore, to understand progeria, it is important to look at the following aspects: history, what
is HGPS, why HGPS occurs, symptoms, and treatment.
I. Being born pre-mature has led me to become fascinated with the medical field and the world.
II. HGPS is a crucial disease and medical breakthrough because it can lead us to understand the
biology and effects of aging.
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4. Works Cited
1. Gordon, Leslie B et al. “Disease Progression in Hutchinson-Gilford Progeria Syndrome:
Impact of Growth and Development.” PEDIATRICS. 2007. 824-832.
2. Kieran, Mark W et al. “New Approaches to Progeria.” PEDIATRICS. 2007. 834-840.
3. Pollex RL, Hegele RA. “Hutchinson–Gilford progeria syndrome.” Clin Genet 2004: 66: 375–
381.
4. Sarkar, P K, and R A Shinton. "Hutchinson-Guilford progeria syndrome.” Postgraduate
Medical Journal. 77.907 (May2001): 312. Gale. California State Univ, Northridge. 25 June 2008
5. Nicolas, Sylvius et al. "Specific contribution of lamin A and lamin C in the development of
laminopathies." Experimental cell research (2008): 1-14. ScienceDirect (Elsevier). California
State Univ, Northridge. 29 June 2008.
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