Researchers, parents and patients meet in Marseille

On Jan 16, the Italian and French research groups that work on Laminopathies met in Marseille. It was a combined meeting for doctors and patients, including parents of children with progeria. ‘Laminopathies’ include all diseases that are caused by a non-functioning Lamin A/C gene, and progeria is one of these.

The meeting was spread over two days: lectures of the first day were meant for physicians and researchers. The second day was also intended for the patients. Some of the lectures second day went very far in the theory and were not easy to follow for families, other presentations were addressed to them.
The main lecture for families with children with progeria was presented by Dr. Annachiara De Sandre-Giovannoli, from the lab of Dr. Nicolas Levy. She first gave an overview of all therapies that have been given in the past, and their results. Next she discussed the new substances that have been developed and in part also already tested in mice with progeria. These substances all focus on the principle to change the RNA from which Lamin A/C is made. The simple summary is that DNA makes RNA, and then RNA makes proteins. Since children with progeria have abnormal DNA, they form abnormal RNA, which leads to a different lamin A/C and an ill-structured Lamina in their cells. If the deviation in the RNA can be corrected, this will not only repair the abnormal Lamin A/C, but will also produce normal functioning Lamin A/C.
There are now a number of substances that can correct this RNA. These substances work well in mice. In mice they show no important side effects. The presented results were really good. The main problem is to ensure that the substances end up in the right quantity at the right place in the body, without the body breaking the substances down. The lab has contacted the company Sarepta, a pharmaceutical company that has a lot of experience with this type of medication (they use them also for the muscle disease Duchenne muscular dystrophy). Researchers and Sarepta work together to find a cure.

Dr. De Sandre-Giovannoli explained what steps should all be taken before one can start with a trial. These are mainly administrative procedures, which usually require many years with an ordinary drug, but because they always ask for extra rush everywhere, they should be able to succeed in about a year. That means that if all goes well, this one trial could start sometime in Spring 2016.

What can the families do in the meantime?

1. For all children the use of statins is and remains useful. Statins can be given by the General Practitioner or paediatrician.

2. Whether it makes sense to use also other medication is very uncertain. The Boston group has offered a trial with Lonafarnib. A small percentage of the children showed some improvement in weight gain and formation of bone and blood vessels. The result were really limited, but there were some results. The Boston group stopped their trial, but still provide Lonafarnib to children with progeria. Children can come to Boston for a complete check-up, and will receive sufficient Lonafarnib for two years, without further checks/travels to Boston. Each family has to decide whether adding Lonafarnib is worthwhile, balancing the burden of travelling and the exams in Boston, plus the subsequent daily taking the medication thereafter, and the limited results that it can potentially offer. There is no general rule here, each family will have to make their own decision in this. The alternative is to use no other drug next to statins, and await the upcoming trial in Marseille. We have currently no new information from Boston and do not know whether there are plans for a new trial as well.

The above gives us in fact mixed feelings: the good news is that important new substances have been developed and even already tested, and these are really promising. The downside is that it all takes longer than we had hoped for. A new trial somewhere early next year, and till that time very limited possibilities (next to statins).

Raoul Hennekam

The program of the meeting in Marseille can be found HERE.