At HRW, we love keeping up to speed on the latest developments in a vast range of therapy areas: and our neuroscience specialist team, HRW Synapse, is no different. With this space hallmarked by evolution, rapidly emerging discoveries, and a stubborn swathe of unknowns, Abigail Graham, Research Manager was blown away by the knowledge, insights, and mysteries on show at this year’s Federation European Neuroscience Societies (FENS) conference in Paris (9th – 13th July 2022). Read on to find out what she learned- including why we need to listen to our gut when it comes to neurological conditions…
This month I had the pleasure of attending the FENS conference in Paris. It’s safe to say that I’m now very tired due to the sheer volume of information that my brain absorbed over the short five-day period. What’s also safe to say is there are hundreds, if not thousands of researchers, scientists and industry experts all working hard to halt the progression of and cure neurological conditions.
I couldn’t possibly tell you everything that I’ve learnt over the past few days – quite simply I could keep writing forever. From clinical advances in Alzheimer’s Disease, Parkinson’s Disease and Huntington’s Disease to ground-breaking research into psychedelics, this conference covered everything. Below are my three key takeaways from the conference this year.
There are still so many unknowns within Neuroscience
Although there are clinical breakthroughs in the pathology of Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Huntington’s Disease (HD) there are still so many unknowns and hypothesis being generated.
Roche Genentech made these unknowns clear during their lectures: they discussed all three of these conditions, highlighting the challenges and opportunities for each. The underlying theme: we do not understand the pathology of the diseases as every patient presents differently with varied symptoms. This means that multiple mechanisms of action (MOA) are being investigated and multiple treatments will be needed to ensure the prevention of progression for all patients. For example:
- Patients with PD will present with varied motor and non-motor symptoms and all progress at different speeds. This means different MOAs might be needed to target different symptoms
- In the case of AD, the pathology alters as the disease progresses, meaning different pharmacological treatments will be needed across a patient’s treatment journey
- For HD, trials focus on targeting the mutant HTT gene, but there are questions marks over whether this is the best approach. Recently, Roche had to stop their phase 3 trial of Tomerisan as it was shown to have worse efficacy and safety vs. placebo. This simply highlights the continued unknowns in this space.
Continued unknowns were also highlighted through the methodologies within early trials: most notably, everywhere I looked were images of mice. Perhaps naively, I didn’t expect this- and my ethics were slightly questioned when scientists discussed hanging a mouse from their tail or causing them to have an alcohol addiction. This was a ‘hot topic’ for debate during the conference: is it time to move away from mouse models and can we really transplant these findings to humans?
But it’s not all doom and gloom
During the conference, I learnt a lot about Spinal Muscular Atrophy (SMA) – a genetic condition which makes the muscles weaker and causes problems with movement. From Type 1 (presenting in infants <2 months, who will never sit up and sadly die before their 2nd birthday) to Type 4 (presenting in later childhood, who live to a normal life expectancy, but may struggle to walk in later life) it was clear that this condition required research and an effective treatment.
Risdiplam (an oral medication) provides this for patients. Early Phase 1 trial data showed Type 1 patients started to restore motor functions like a ‘normal’ child: they reached motor milestones (e.g., sitting up) within the ‘normal’ time window for a child. Without treatment these children would have died before their second birthday.
It was also clear during the conference that early diagnosis of neurodegenerative diseases is vital. Sadrine Humburt discussed how the early detection of the mutant HTT gene in pre-natal babies could help to stop the progression of Huntington’s Disease (HD) later in life.
Finally, ‘ground-breaking research or treatment’ was a term that I heard multiple times throughout the conference. For me, this was most evident in the workshops and lectures about psychedelics (e.g., 5-MEO-DMT, LSD, Psilocybin) and dissociative (e.g., Ketamine) compounds. These compounds have been shown to be effective against multiple stress related conditions (e.g., depression, anxiety, PTSD). They can ‘open up’ the brain structures and restore cognitive function. But they are contentious and clinical studies are in their infancy. I heard they are ‘revolutionary’ vs. gold standard treatments currently used (e.g., SSRIs) but little is known about the long-term duration of the treatments. I won’t go into too much detail about this contentious subject, as we have an internal debate on the topic which covers the benefits and watchpoints in a lot more detail. LINK.
The role of gut microbiomes
A continued subject which resurfaced during the conference was the role of the gut and our diet and how this can increase risk factors for neurological conditions. This ranged from how obese mothers are more likely to have a child with autism and how binge drinking can lead to a psychological dependency due to a leaky gut.
Specifically, Mauro Costa-Mattioli discussed how babies from obese mice mothers were more likely to be socially impaired vs. those from non-obese mothers. He discussed how his findings suggested how a faecal matter transplant (FMT) from non-socially impaired mice to socially impaired mice significantly reduced the social deficit. He has now taken these findings one step further and conducted a FMT from non-autistic children to those with autism. To say the letters which he had received from parents because of this study were emotional is quite simply an understatement. Phrases such as ‘social abilities skyrocketed’ and ‘ability to have a relationship and a normal life’ encapsulate the overall themes: it was clear that this FMT had really contributed to helping these children become less socially isolated.
Furthermore, evidence was also presented to suggest that Alcohol Use Disorder (AUD) – defined as a chronic relapsing brain disease, resulting in compulsive use of alcohol, loss of control with intake of alcohol and negative emotional state – can also be impacted by gut microbiomes. Specifically, research found increased veionella bacteria in the gut can predict drinking and a FMT can reduce the reliance of alcohol in patients. What this tells us is that researchers and the neuroscience community are looking elsewhere for causes and treatment for neurological disorders.
The above simply scratches the surface in terms of what I learnt during the FENs conference: I haven’t touched on my findings in Epilepsy, Multiple Sclerosis (MS) or Migraines. As mentioned, I’ve had to be selective otherwise I could simply keep writing forever. However, please get in touch if you have any questions or if you want to learn more about the above!
By Abigail Graham