PROJERIA

What is Progeria?

Progeria is a genetically dominant disease which is caused by a single mutation in DNA resulting in production of Progerin.

Progeria is an extremely rare, fatal genetic condition. The word Progeria comes from the Greek progeros which means prematurely old. The classic type of Progeria is HGPS (Hutchinson-Gilford Progeria Syndrome). Progeria was first described in an academic journal by Dr. Jonathan Hutchinson in 1886 and Dr. Hasting Gilford in 1897- both in England.

It is a genetic condition characterized by the dramatic, rapid appearance of aging beginning in childhood. Affected children typically look normal at birth and in early infancy, but then grow more slowly than other children and do not gain weight at the expected rate (failure to thrive).

Progeria in the World

A very rare disease in this world which affects 1 in four million people is Progeria. Till today 100 cases are diagnosed with progeria all over the world and there could be more.

Causes

Mutations in the LMNA gene cause Hutchinson-Gilford progeria syndrome. The

LMNA gene provides instructions for making a protein called lamin A. This

protein plays an important role in determining the shape of the nucleus within

cells. It is an essential supporting component of the nuclear envelope, which is

the membrane that surrounds the nucleus. Mutations that cause Hutchinson

Gilford progeria syndrome result in the production of an abnormal version of

the lamin A protein. The altered protein makes the nuclear envelope unstable

and progressively damages the nucleus, making cells more likely to die

prematurely. Researchers are working to determine how these changes lead to

the characteristic features of Hutchinson-Gilford progeria syndrome.

Symptoms

• Dwarfism / Limited Growth

• Alopecia or baldness

• Small face and a pinched nose

• Small jaw in comparison to head size

• Delayed tooth development

• Aged looking, wrinkled skin

• Loss of eyebrows/ hair

• Stiff joints / limited range of motion

• Frequent hip dislocation

• Premature Arteriosclerosis

• Cardiovascular Problems

• No sexual maturation

Treatment• Till date, there is no particular treatment for Progeria.

• First-Ever Progeria Clinical Drug Trial for Progeria started in Boston by Progeria Research Foundation in May 2007 which involved 28 children of age 3 to 15 years from 16 countries across the world.

• Since the start of the first trial, researchers identified two additional drugs that, when used in combination with the current drug being tested, may provide an even more effective treatment than the single drug.

• The Triple Drug Trial is much larger than the first, involving 45 children from 24 countries: most of the 28 in the first trial, and those that were either too young for the first trial or not known to PRF during enrolment for that trial.

• Every child participating in the study showed significant improvement in weight gain ability, bone structure or flexibility of blood vessels.

Results of the Drug Trial

•Weight: one in three children demonstrated a greater than 50% increase in annual rate of weight gain, or switched from weight loss to weight gain, because of increased muscle and bone mass.

•Bone Structure: Bone rigidity improved to normal level after FTI treatment.

•Cardiovascular: Arteries stiffness, associated with atherosclerosis, decreased by 35%. Vessel wall density also improved.

Social Perception of People Towards Progeria

For people, they have different perception to see this disease such as some people see it as something weird or some are quite sympathetic towards these children and some fear to these children. Sometimes these children experience some really weird response from the audience because people stare at them as if they are from outside this world. Sometimes, at some parts of world such as India, people fill this as something to be forbidden. There is a patient named Priya from India who suffered loneliness in her village because people fear to even touch her.

Attitude of Progeria Patients Towards Life

In almost all the cases it is a very good thing that

these children are very positive about their life.

They live life like all other normal children. For

them, Progeria is not that they have in their life,

rather it is just a small part of their life which they

try to overcome by behaving normally and live

normally among others.

Some Progeria Patients • Sam Berns

On 23rd October 1996 Sam Berns came into this world but

with a single mutation in his DNA. He appeared healthy

when he was born. But within a year, his parents suspected

something was wrong. He was diagnosed at 22 months.

Sam died last Friday at the age of 17—an unusually long

life considering that most progeria patients die at an average age of 13. Before

he died, he built entire Lego towns, earned middle-school awards, played in his

high-school marching band, went to the prom, and dreamed of going to MIT in

hopes of becoming an inventor, according to the HBO documentary Life

According to Sam.

•Zack Pickard

Zack is a feisty and lively three year old boy. He goes to day

care school each day and fits in perfectly with the other three

year olds. He enjoys playing with his trucks and cars, and

he loves to paint and draw. His favourite thing to do is to ride

in an airplane and he loves to ride the bus. Zack has an infectious smile

and it doesn't take long for him to steal your heart. He tends to bring

attention to himself no matter where he is.

Progeria Patients and Their Parents

Talking about parents, it is very encouraging to see their positive attitude towards their children. They try their level best to take care of their children because every minute spent with them are precious. Many of them also started working towards future to help the children suffering from progeria all over the world. One of its greatest examples is Progeria Research Foundation established by Dr. Leslie Gordon and Dr. Scott Berns. Their son Sam Berns was born in 23rd October 1996 and died at the age of 17 on 10th January 2014 suffering from Progeria.

Progeria Research Foundation

•Research foundation established by Dr. Leslie B. Gordon , Dr. Scott Berns and Audrey Gordon in 1999 in Boston.

•Before this organisation there was no research going on for Progeria.

• PRF was the driving force behind finding the gene responsible for Progeria. A group of leading scientists from PRF’s Genetics Consortium was able to isolate the Progeria gene in 2003.

• PRF started the drug trials as a treatment for progeria in 2007 and also the three drug trials in 2009.

References

• BMJ. (1974). Premature Aging Syndromes. The British Medical Journal, Vol. 4, No. 5943, 489-489

• Cao, K., Capell, B.C., Erdos, M.R., Djabali, K., Collins, F.S. (2007). A Lamin A Protein Isoform Over expressed in Hutchinson-Gilford Progeria Syndrome Interferes with Mitosis in Progeria and Normal Cells. Proceedings of the National Academy of Sciences of the United States of America, ,Vol. 104, No. 12, 4949-4954

• McClintock, D. Gordon, L.B. Djabali, K. (2006). Hutchinson-Gilford Progeria Mutant Lamin A Primarily Targets Human Vascular Cells as Detected by an Anti-Lamin A G608G Antibody. Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 7, 2154-2159

• Travis, J. (2003). Genetic clue to aging. Science news, Vol. 163, No. 17, 260-261