Montreal patient undergoes genetic procedure for frontotemporal dementia

It was a first. In Canada, 2 doctors from the Montreal Neurological Institute performed A genetic procedure this week on a patient living with Frontotemporal dementia in hopes of slowing down the progression of the disease. You may have heard of the disease because of actor Bruce Willis. He was diagnosed with it a couple of years ago. Doctor Simone Duchamp is a neuropsychiatrist and clinician scientist rather at The Neuro and one of the doctors involved. Thank you so much for joining us today. Thank you for the invitation. First of all, frontotemporal dementia. It hits people generally under the age of 65, anywhere from 4050 up to 65, and the symptoms are devastating. Can you describe them for us? Yeah, that’s correct. So it’s it’s an early form of dementia, as you were saying, that starts usually in adults at a younger age than we would expect for dementia. So in the 40s and the 50s it attacks the the front part of the brain, so the frontal lobes and the temporal lobes, which will give us usually some either profound behavioural changes that are progressive over time. So people will lose inhibition, motivation, empathy for others and they can also have changes in language. So they lose their capacity to say words, to express themselves, to understand language. So what we call aphasia, so usually some combination of aphasia and behaviour changes and do we know what causes it? In one out of five people, we can identify a genetic mutation, which means it’s a hereditary form that they received from their parents. That still leaves about 80% of patients for whom we do not know why this particular individual developed frontotemporal dementia at a young age. But in the one out of five people with a genetic mutation, then we can know exactly what’s the cause. OK, so the patient that you operated on this week had the hereditary form was in that 20%. Then what? What? What is the procedure exactly that you performed and what are you hoping to achieve? So this was a patient with a a frontal temporal dementia due to a mutation in the PRO granulin gene. So this is a genetic defect the patient was born with that he received from his family that leads to a lack of production of a key protein in the brain called granolin. For some reason, this does not cause problems early on in development or young adulthood. But over times, the lack of this protein called granolin, starts triggering a cascade in the brain, damaging the frontal and temporal lobe, leading to the symptoms. We discussed aphasia and some other patient behavioural changes. So what we did was a research study with a new technology from a company called Passage Bio that essentially is able to insert the missing genetic material directly in the brain and then the the patient’s brain will start using that new gene to produce the missing protein. So it’s a very early stage study. He was the 4th patient in the world to receive that therapy, which is injected with a neurosurgery that a colleague performed at the base of this call to go inject this in the fluid in which the brain is bathing. And the procedure was done on Tuesday without any complication. Wow, it is fascinating. So how is your patient doing and when will you see whether this treatment has done what you’re hoping it has done? The procedure is technically complicated because we’re very close to the brain, but if we do it properly, it is a very safe procedure. We do it under CT scan, so imaging guidance, what we’re hoping now is that this new drug will go into the brain cells and then the patient will start producing more of this granulin protein. And the early indications we have from the other few patients who receive it is that it seems to be working. So in this patient in the next few weeks, the next few months, we will be using what we call lumbar puncture where we take a little bit of fluid from the lower back to see if the protein is increasing. And that could mean the medication is biologically working where with what we are hoping for patients is that this could at least slow down the progression of their disease. So we are not expecting a reversal because the symptoms are caused by a damage to nerve cell that is probably irreversible. But we’re hoping to slow the progression or even maybe stop the progression because it is a disease that in in the current state of affairs without any treatments always progresses over a few years. And the the long term goal is even that if this works in patients with mild symptoms, we could even do research to give the treatment to carriers of the mutation even before they start having symptoms to really push back the onset or maybe even prevent it. So that that’s also very encouraging because this is hereditary for family members I suppose like your patient if they have children. Yes, I mean I would say that’s the main reason why patients with these diseases are willing to participate to research like this which takes a fair amount of courage because it’s it’s a very experimental procedure. There is hope in those families that maybe we can slow the progression of this patient and the upcoming few ones who will receive it. But really, what would be the the game changer is to be able to completely prevent this for their children’s generation? It’s fascinating. Dr. Dushan, thank you so much for joining us. Thank you.