HGPS(Progeria disease)

Progeria

Mahtab Abedi

Medical student at birjand university

2015,March

• Progeria (HGPS), also known as

Hutchinson-Gilford syndrome,

is an extremely rare

• progressive genetic disorder that

causes children to age rapidly

What is progeria ?

beginning in their first two years of life

Signs & symptoms

Slowed growth , below average height & weight

Hardening & thightenning of skin

Narrowed face Delayed & abnormal tooth formation

Head disproportionality large for face Some hearing loss

Prominent eyes Lose of fat under the skin & loss of muscle mass

Hair loss, including eyelash & eyebrow Fragile bones

Visible veins Stiff joints

Physicalissues

Healthissues

Most children with progeria die of complications related to atherosclerosis, including:

cardiovascular problems cerebrovascular problems

heart attack stroke

Other health problems frequently associated with aging — such as arthritis, nearsightedness and increased cancer risk — do not develop as part of the course of progeria

blood vesseles that

supply

LMNA is not expressed by the brain cells, so the gene mutation does not affect the brain

Children with Progeria are intelligent and full of energy just like other kids their age.

Epidemiology and History of Progeria

Until …..23 October 1996

Dr. Scott BernsDr. Leslie Gordon

1998 : sam’ s disease was dignosed.(at 22 months)1999: Drs. Leslie Gordon and Scott Berns, established The Progeria Research Foundation2003 : the cause of disease was discovered.2012: the first-ever drug treatment was discovered.

What is the cause of Progeria?

What is the cause of Progeria?

HGPS is caused by a mutation in the gene called LMNA (pronounced “lamin-a”).

The LMNA gene produces the lamin A protein which is the structural scaffolding that holds the nucleus of a cell together.

The abnormal lamin A protein that causes Progeriais called progerin. Progerin makes the nucleus unstable. That cellular instability leads to the process of premature aging and disease in Progeria.

Normal cell

Progeria cell

Tests and diagnosis

• Doctors may suspect progeria based on signs and symptoms characteristic of the syndrome. A genetic test for LMNA mutations can confirm the diagnosis of progeria.

• What are FTIs? Farnesyltransferase inhibitors, or FTIs, are a class of drugs that can reverse an abnormality in Proeria cells.

Lonafarnib, a farnesyl transferase inhibitor

How will they work in Progeria?

• The protein that we believe is responsible for Progeria is called progerin.

• In order to block normal cell function and cause Progeria, a molecule called a “farnesyl group” must be attached to the progerin protein. FTIs act by blocking (inhibiting) the attachment of the farnesyl group onto progerin. We believe that if the FTI drug can effectively block this farnesylgroup attachment in children with Progeria, then progerin may be “paralyzed” and Progeria may be improved.

in September 2012 when the first-ever drug treatment was discovered. Every child in the clinical trial involving Lonafarnib, a farnesyltransferase inhibitor, showed improvement in one or more of four ways:

• gaining additional weight

• better hearing

• improved bone structure

• most importantly, increased flexibility of blood vessels

Treatment didn't come soon enough for Sam. But he and his parents spent his short, remarkable lifetime pushing science and understanding forward.

Sam Berns

23/10/96 - 10/01/14