Cutting-edge gene therapy could help slow young-onset Frontotemporal Dementia
Individuals with FTD due to progranulin mutation sought for this study
December 11, 2023
It sounds like something out of science fiction: a neurosurgeon injecting a treatment into a patient’s neck so that it crosses the blood brain barrier. But this isn’t a movie, it’s a new gene therapy — a promising line of treatment that is being explored as a potential avenue to treat dementia.
The Neuro is the only site in Quebec taking part in a Phase I clinical trial testing this potentially groundbreaking treatment that hopes to slow or stop an inherited form of Frontotemporal Dementia (FTD). The study is the first gene therapy trial for dementia conducted in Canada.
The trial is specifically for patients with FTD who have a mutation in the GRN gene, that stops them from producing enough progranulin — a protein crucial for brain function.
“Most forms of dementia are multifactorial; it is a complicated disease, and addressing one factor may not make a substantial impact. There is a much higher likelihood that we will find cure for a genetic form of the disease that has a single well-identified cause. If you can impact that factor, the hope is that you can dramatically slow it down or reverse the dementia. That’s what we are looking to do here,’’ says Dr. Simon Ducharme, a neuropsychiatrist and clinician-scientist at The Neuro (Montreal Neurological Institute-Hospital) who is the principal investigator for the study in Montreal.
The Alzheimer Society of Canada estimates that 5 to 10% of all dementia cases are FTD – the disease with which Bruce Willis was recently diagnosed. It is a young-onset dementia and the most common form in people under 60. Early signs including marked changes in personality and judgment, followed by increasing problems with language as well as movement disorders, such as tremors, muscle stiffness and slow movement. The average survival after neurocognitive changes is just 8 years.
Genetic mutations make up about a quarter of cases of FTD, of which 5-10% are due to GRN mutations. Almost all individuals with the GRN mutation will go on to develop the disease. And because this is a genetic version of the disease, affected individuals have a 50% chance pass it down to each of their children.
The treatment being tested is viral vector-based gene therapy. Viral vectors have been increasingly used in the past 5 years. They are an inactivated virus which is used as a vehicle to carry a working gene to a cell.
“This is very exciting; it is true gene therapy. It is a one-time dose and theoretically the effect is dramatic and long lasting, similar to the treatments we have seen approved recently for Spinal Muscular Atrophy (SMA),” says Dr. Ducharme.
The therapy being tested hopes that by delivering a working copy of the GRN gene, the body can then go on to increase the production of progranulin protein.
“The idea is that even if the disease is present the progression could be stopped in its tracks. You could have a patient who has progressed but who would benefit by maintaining their quality of life without further deterioration. One day, if treatments like this one are successful, the treatment might extend to those with the mutation prior to symptom onset to spare them from developing this condition,” concludes Dr. Ducharme.
Individuals between 35 and 75 diagnosed with FTD can reach out to the Clinical Research Unit at The Neuro at 514-398-5500 or neurocog-CRU.firstname.lastname@example.org. Travel from outside the province can be covered by the trial.
To participate in this study, contact email@example.com.
Tiba ya jeni ya kisasa inaweza kusaidia kupunguza dementia ya mbele ya kipaji ya vijana kutokana na mabadiliko ya progranulin, inadai utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti wa utafiti. Lakini hii si filamu, ni tiba mpya ya jeni - mstari wa matibabu unaotarajiwa ambao unachunguzwa kama njia inayowezekana ya kutibu ugonjwa wa akili. Kituo cha Neurology cha Quebec kinafanya majaribio ya kliniki ya awamu ya kwanza ya matibabu ya kuharibu au kuzuia aina ya dementia ya mbele ya kiungo cha mbele. Utafiti huo ni wa kwanza wa matibabu ya jeni kwa ugonjwa wa akili uliofanywa nchini Kanada. Utafiti huo unawafikia wagonjwa wenye ugonjwa wa FTD ambao wana mabadiliko katika jeni la GRN, ambayo huwazuia kutengeneza progranulin ya kutosha - protini muhimu kwa kazi ya ubongo. <unk> Aina nyingi za dementia ni multifactorial; ni ugonjwa tata, na kushughulikia sababu moja inaweza kufanya athari kubwa. Kuna uwezekano mkubwa zaidi kwamba tutapata tiba ya aina ya ugonjwa wa urithi ambao una sababu moja tu iliyojulikana vizuri. Ikiwa unaweza kuathiri sababu hiyo, matumaini ni kwamba unaweza kupunguza au kubadilisha ugonjwa wa akili. "Hiyo ndiyo tunayotafuta kufanya hapa, ""anasema Daktari Simon Ducharme, daktari wa magonjwa ya akili na mwanasayansi wa kliniki katika The Neuro (Montreal Neurological Institute-Hospital) ambaye ni mtafiti mkuu wa utafiti huko Montreal." Shirika la Alzheimer's Society la Canada linakadiria kuwa asilimia 5 hadi 10 ya watu wote wenye ugonjwa wa akili ni wenye ugonjwa wa FTD, ugonjwa ambao Bruce Willis aligunduliwa kuwa nao hivi karibuni. Ni ugonjwa wa akili unaotokea kwa vijana na ni wa kawaida kwa watu walio chini ya miaka 60. Dalili za mapema ni pamoja na mabadiliko makubwa katika utu na uamuzi, ikifuatiwa na kuongezeka kwa matatizo na lugha na vile vile matatizo ya harakati, kama vile kutetemeka, misuli rigidity na harakati polepole. Kwa mfano, wastani wa maisha baada ya mabadiliko ya neurocognitive ni miaka 8. Mabadiliko ya maumbile hufanyiza karibu robo ya visa vya FTD, ambayo 5-10% ni kwa sababu ya mabadiliko ya GRN. Karibu watu wote walio na mabadiliko ya GRN wataendelea kupata ugonjwa huo. Kwa sababu ya aina ya ugonjwa huu, watu walioathiriwa na ugonjwa huo wana uwezekano wa 50% wa kuupatia mtoto wao. Matibabu yanayopimwa ni tiba ya jeni inayotegemea virusi. Vector ya virusi imekuwa ikitumika zaidi katika miaka mitano iliyopita. Ni virusi visivyofanya kazi ambavyo hutumiwa kama chombo cha kubeba jeni linalofanya kazi kwenye chembe. <unk>Hii ni ya kusisimua sana; ni tiba ya kweli ya jeni. "Ni kipimo cha mara moja na kwa nadharia athari ni ya kuvutia na ya kudumu, sawa na matibabu ambayo tumeona kupitishwa hivi karibuni kwa Spinal Muscular Atrophy (SMA) "" anasema Dk Ducharme." Tiba hiyo inatarajiwa kuwa kwa kutoa nakala ya kazi ya jeni la GRN, mwili unaweza kuendelea kuongeza uzalishaji wa protini ya progranulin. <unk>Wazo ni kwamba hata kama ugonjwa upo maendeleo yanaweza kusimamishwa katika nyimbo zake. Mgonjwa anaweza kuwa na maendeleo ya afya lakini kufanikiwa katika kudumisha ubora wa maisha yake bila kuzorota zaidi. Siku moja, ikiwa matibabu kama haya yanafanikiwa, matibabu yanaweza kupanuka kwa wale walio na mabadiliko kabla ya mwanzo wa dalili ili kuwaokoa kutokana na kuendeleza hali hii, "anahitimisha Dk Ducharme. Kwa wale wenye umri wa kati ya miaka 35 na 75 na ugonjwa wa FTD, unaweza kuwasiliana na Kituo cha Utafiti wa Kliniki katika Neuro kwa 514-398-5500 au neuroclinic.cru.firstname.lastname@example.org. Safari kutoka nje ya mkoa inaweza kufunikwa na jaribio. Ili kushiriki katika utafiti huu, wasiliana na email@example.com.