View Full Version : Teenager's sickle cell reversed with world-first therapy

Jean M
03-03-2017, 12:10 AM

A French teenager's sickle cell disease has been reversed using a pioneering treatment to change his DNA. The world-first procedure at Necker Children's Hospital in Paris offers hope to millions of people with the blood disorder. Scientists altered the genetic instructions in his bone marrow so it made healthy red blood cells.
So far, the therapy has worked for 15 months and the child is no longer on any medication.

Sickle cell disease causes normally round red blood cells, which carry oxygen around the body, to become shaped like a sickle. These deformed cells can lock together to block the flow of blood around the body. This can cause intense pain, organ damage and can be fatal. The teenager who received the treatment had so much internal damage he needed to have his spleen removed and his hips replaced. Every month he had to go into hospital to have a blood transfusion to dilute his defective blood.

But when he was 13, doctors at the Necker Children's Hospital in Paris did something unique. Doctors removed his bone marrow - the part of the body that makes blood. They then genetically altered it in a lab to compensate for the defect in his DNA that caused the disease. Sickle cell is caused by a typo in the instructions for making the protein haemoglobin, which is densely packed into red blood cells. A virus was used to infect the bone marrow with new, correct instructions. The corrected bone marrow was then put back into the patient.

The results in the New England Journal of Medicine showed the teenager has been making normal blood since the procedure 15 months ago.

03-03-2017, 06:55 AM
Sickle cell is caused by a typo in the instructions for making the protein haemoglobin

03-03-2017, 09:18 AM

There is a particular reason why it is so prevalent in Africa. It gives protection against malaria. The trade-offs of mutations!

06-05-2018, 12:37 AM
Yup, Africa is the typical textbook example of environmental natural selection, in which having a genetic mutation proves more beneficial to an organism in the given environment as opposed to having a normal copy of the gene (survival advantage).

However, you only have protection against malaria if the individual in questions is a carrier (one copy of the gene).
It has been somewhat of a mystery as to what exactly it is that allows sickle cell carriers to be resistant to malaria [many speculated whether it somehow directly effected the organisms (plasmodium-malaria causing parasite) ability to infect the host's cell], but a study in 2011 was able to describe the exact physiological process by which sickle cell individuals confer protection from malaria; the caveat? it was observed in mice:

"Through a series of genetic experiments, Ana Ferreira was able to show that the main player in this protective effect is heme oxygenase-1 (HO-1), an enzyme whose expression is strongly induced by sickle hemoglobin. This enzyme, that produces the gas carbon monoxide, had been previously shown by the laboratory of Miguel Soares to confer protection against cerebral malaria. In the process of dissecting further this mechanism of protection Ana Ferreira demonstrated that when produced in response to sickle hemoglobin the same gas, carbon monoxide, protected the infected host from succumbing to cerebral malaria without interfering with the life cycle of the parasite inside its red blood cells." (Science News: Mystery solved: How sickle hemoglobin protects against malaria).

An article on New Scientist titled, How sickle-cell carriers fend off malaria provides better insight on the physiological phenomena.

As of yet, I am unaware of any new findings around this topic.