26 November, 2020

Dear SCADaddles:

Re: 2020 Update

It’s been suggested that if this year was a “belt” it would have been made of “barbed wire”! I do hope that, at least from a SCAD perspective, it hasn’t been too challenging for everyone.

Despite Covid, we have been very fortune to be able to continue our work with relatively few interruptions. Thanks to our politicians listening to our scientists and to the people of Australia for their willingness to follow guidelines, we have been much more fortunate than those in most other countries. Nonetheless, we have sadly lost almost a thousand people to SARS-CoV-2.

My thanks to everyone involved in our SCAD studies who took time during this difficult year to help by giving us medical history information and providing biological samples.

The good news is that the vaccines being developed for Covid are looking promising and, importantly, we have made some exciting SCAD progress this year.

First, in a paper published in the prestigious medical journal, Circulation: Genomic and Precision Medicine, together with collaborators in the UK, we reported on genetic links between SCAD and connective tissue disorders and familial blood vessel problems. We found that several people who have had a SCAD, have a mutation in a gene that is associated with these conditions. Sometimes the SCAD sufferer also has the connective tissue or blood vessel problem, although usually not. These studies also suggest strongly that, unfortunately, it is very likely that changes in many different genes might predispose to SCAD.

Second, we are currently following up on these studies in further, more detailed investigations exploring the relationship between SCAD and other inherited collagen and blood vessel disorders, which will be reported in another paper soon to be submitted for publication.

An unexpected outcome of these studies is the discovery of a previously unrecognised gene change that, although of unclear significance for the development of SCAD, might explain a very serious disorder in the child of a SCAD sufferer, which has gone unexplained since the child was born 13 years ago, and might be of directly relevant for the sister of this child, should she have children herself in the future.

Third, we have been collecting DNA samples from people in families where more than one person has had a SCAD. Often when a condition runs in a family it can be easier to determine the genetic cause than in those with no other family members involved. So far, 17 of our SCAD sufferers have a family history of SCAD, and we are working to recruit as many people from these families as possible, including those who have not had SCAD. We have now determined the entire gene sequence of most of these people and this data, which is massive as it involves six billion bits of information for every person, is now being analysed by our bioinformatics team, lead so ably by my colleague, A/Prof Eleni Giannoulatou. From the analyses done so far, we are cautiously very excited as we believe we have found gene changes that very likely explain the predisposition to SCAD in two families, although much work remains to be done to really prove that this is the case.

Fourth, we have determined the entire gene sequence of 11 people and as many of their family members as possible, who have had a SCAD and also have a family history of aortic dissection. This data will be used to see if there are similar gene changes in those suffering from a SCAD and their relatives who have had an aortic dissection; studies that will be reported in another paper. Our thanks to all these SCAD sufferers and their unaffected family members for their participation.

Fifth, together with colleagues in the UK, the Mayo Clinic and Mount Sinai Medical Center in the US and in Paris, we are currently undertaking a world-wide study of SCAD genetics that will involve ~2,500 cases, looking for gene variations that may be common amongst the group.

Finally, a review of SCAD and fibromuscular dysplasia (FMD) that we wrote has been published in the journal Heart, Lung & Circulation and has been very well received. We would be pleased to provide a copy of the paper for anyone who is interested*.

In addition to these genetic studies, we are continuing our cell work. Although this is a long slow process, we have made cell lines from seven SCAD patients and we are comparing them to cells obtained from people of the same age and sex who have not had SCAD, to understand how they might explain the dissection that occurs with SCAD.

In March this year I stepped down as the Director of the Victor Chang Cardiac Research Institute that I have been privileged to lead since its inception 26 year ago but continue to be busy with research and I still see heart patients. We are very fortunate to have attracted Prof Jason Kovacic back from the US to take over as Director. Jason is an outstanding cardiologist and researcher, who completed a PhD many years ago working in my laboratory. He is widely regarded as a world leader in FMD as well as being actively involved in SCAD research, so will help to further enhance our SCAD studies.

So again, most sincere thanks to everyone in the SCAD community for your support. Wishing everyone a relaxing SCAD-free Christmas and a Happy New Year.

Kind regards,

 

Robert M Graham, AO, MD, FAA, FAHMS

Consultant Cardiorenal Physician;

Head, Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute (VCCRI); Des Renford Professor of Medicine, UNSW

 

Victor Chang

Cardiac Research Institute

*Please send a request to SCAD@victorchang.edu.au