REVERSE RETT AT THE BPNA MEETING IN EDINBURGH

by Rachael Stevenson, Reverse Rett CEO

In January, I attended the annual British Paediatric Neurology Association (BPNA) meeting in Edinburgh.

It was a great week to be there following the announcement by Neurogene that they have received FDA clearance for a clinical trial of their gene therapy product, NGN-401. FDA approval means that Neurogene can now work towards starting their gene therapy trial in the USA. We expect further news about this later in the year.

Those with older children with Rett Syndrome will know that Edinburgh has been at the heart of Rett Syndrome research for more than three decades because of the work of Sir Professor Adrian Bird, who first identified the Mecp2 protein in the early 90s. (1. Lewis et al., 1992)

At the time, no one knew that the protein played a role in Rett Syndrome.

Whilst it was many miles away in Texas, that Professor Huda Zoghbi's lab discovered that mutations in the MECP2 gene (which makes Mecp2 protein) cause Rett Syndrome (2. Amir et al., 1999), it was back in Edinburgh, only 8 years later, that Professor Bird’s lab showed Rett Syndrome to be reversible in mouse models of even late-stage disease, (3. Guy et al., 2007)

Over the last two decades, Prof Bird has worked collaboratively with Rett researchers worldwide via the Rett Syndrome Research Trust (USA) to help progress his basic laboratory discoveries into disease modifying treatments like gene therapies. Professor Stuart Cobb, whose lab is also now at Edinburgh University, was one of the co-authors on the original reversal paper in 2007. Over the last decade, he has been part of the RSRT Gene Therapy Consortium, heavily financially supported by Reverse Rett. Prof Cobb is now Chief Scientific Officer at Neurogene.

It's wonderful to meet up with both of these world renowned scientists at the BPNA conference and also, such a sign of the times that both were present and involved with this clinically-focused meeting.

Also at our meeting, a third co-author on the 2007 reversal paper, Dr Jim Selfridge, who has recently moved from the Bird Lab to the Cobb Lab to further his interest in the more translational aspects of his work.

At Reverse Rett, we have two Scottish trustees, Kate McMaster and Catherine McKinney, who were both also present at the meeting.

The meeting itself was more useful than I had imagined Rather than having a charity stand in a separate room which clinicians had drag themselves away from their colleagues, coffee and snacks to visit, I decided to attend as a participant myself. This meant that not only could I learn from the wealth of information and learnings being shared in the sessions, I was also able to mingle with Neurologists and their colleagues from all across the UK, sharing information about our work at Reverse Rett and especially about the Rett Registry UK This is important because it often neurologists that diagnose our children with Rett Syndrome and we want them to tell families and caregivers from the outset, to sign up.

But why were Reverse Rett at the British Paediatric Neurology Association meeting in the first place? I hear you ask.

As anyone who cares for a family member with Rett Syndrome can attest, doctors are particularly difficult to pin down Due to our work recruiting for and supporting UK clinical trials, we have regular contact with key UK Rett clinicians, but our interactions are usually tightly focused on the specific trial they are involved with I wanted a little more time with them to discuss their thoughts on emerging treatments, more UK trials and how and where treatments demonstrated to be effective might be delivered in the UK.

Overwhelmingly, my sense of the audience of the BPNA meeting was that these are dynamic, treatment-focused clinicians who were there to learn about new research and innovative best practises that they could implement with their own patients. Some of the talks were from clinicians working in disease groups which now have approved gene therapies. There was a lot to learn from them about planning and implementation, as well as some of the challenges facing patient, families and patient organisations when disease modifying treatments become available.