Huntington is a rare, but dreaded hereditary disease, transmitted by a single defective gene, which leads to irreversible degeneration of the brain. Patients, often diagnosed in adulthood, gradually lose control of their movements, their cognitive capacities and their autonomy, without real therapeutic hope so far. This fatality could be questioned. For the first time, gene therapy shows that it is possible to slow down 75 % – the clinical increase in the disease.
Genetic disease with devastating consequences
Huntington's disease is a rare but formidable hereditary neurodegenerative pathology. It results from a mutation in the gene Htt Located on chromosome 4, responsible for the production of a protein called Huntingtine. In the event of mutation, this protein becomes toxic, accumulates in neurons and causes their progressive degeneration. The disease prioritizes the brain regions involved in the control of movements, cognitive functions and emotions.
The first symptoms generally appear between 30 and 50 years old. They include mood disorders (irritability, anxiety, depression), involuntary movements called chores, alteration of fine motor capacities, then progressive cognitive disorders. The evolution is inevitable and leads, on average, to death between 15 and 20 years after the first signs.
The transmission follows an autosomal dominant mode. A single carrier parent is enough to transmit the mutation, with a risk of 50 % for each child. About 6,000 to 10,000 people are currently affected in the United Kingdom, reports the Guardian. But it is estimated that 20,000 others are carrying without knowing it. The fear of diagnosis is such that only a minority chooses to be tested. Especially because no treatment modifying the evolution of the disease exists.
Until recently, therapeutic options were therefore limited to the management of symptoms (antidepressants, antipsychotics, physiotherapy) without any effect on the course of the disease. This context explains the very strong emotional impact aroused by the announcement of the first results of AMT-1130 treatment. As Professor Sarah Tabrizi, Director of Huntington's Disease Center underlines at the University College London (UCL): “ We had never had an option to slow down the disease. Today it changes. ”
A unique treatment targeting the biological cause of Huntington
Experimental AMT -130 treatment represents a new therapeutic class: intracerebral gene therapy. Its objective is clear: to deactivate the production of the changing Huntingtine protein that causes neural degeneration. This approach therefore does not aim to alleviate symptoms, but to interrupt the pathological process at its source.
Technology is based on a viral vector-an adeno-associated virus (AAV)-modified to be harmless. It serves as a carrier to introduce a therapeutic DNA fragment into the cells. This code fragment for a micro-ARN designed to specifically block messenger RNA responsible for the production of toxic Huntingtine. This mechanism is called interference by RNA (RNA Interference). It is well known in molecular biology, but has never been used on this scale for Huntington.
© UCLHTwo cerebral scanners side by side. The one on the left shows a healthy brain, the one on the right shows a loss of brain matter due to the death of neurons in Huntington's disease.
Treatment administration requires neurosurgery from 12 to 8 pm. Under real -time MRI control, two microcatheters are introduced into the brain to precisely target the cauded nucleus and the putamen, the first regions affected by the disease. The infusion is very slow. The viral vector should be allowed to penetrate the cells without triggering an excessive immune reaction.
The unique Dutch biotech, in collaboration with the Tabrizi teams at UCL and Wild at UCLH, led this intervention on 29 patients in a multicenter trial. The approach is based on a single injection. Therapeutic DNA remains active in long-term neural cells, according to PrD Ed Wild, neurologist and co-responsible for the test. “” The effect should be permanent, since neurons are not renewed as blood or skin cells ».
A clinical slowdown confirmed by several markers
Three years after the intervention, the clinical data available indicate that patients who have received a high dose of treatment saw the increase in their slower disease by 75 %. This measure is obtained from a composite score evaluating motor function, cognitive capacities and autonomy in daily activities.
To understand this data, you should know that Huntington's disease normally causes a rapid and measurable decline on these three dimensions. Treated patients have presented a much slower stabilization or decline than unsolved patients. This is equivalent to four years of clinical profits for a year of usual progression. In some cases, the results were spectacular. A patient who left her job was able to return to work after treatment, according to Professor Wild.
The biological effects are also documented. The level of neurofilaments in cerebrospinal fluid was significantly reduced in treated patients. This liquid constitutes a biomarker of neuronal death. This data suggests real protection of neurons. In comparison, this rate should have increased by a third party in the absence of treatment. As naturally happens with the evolution of the disease.
On the tolerance side, the undesirable effects remain moderate. Some patients have presented headache and transient confusion, linked to post-viral inflammation. But these effects have been treated effectively by corticosteroids or have disappeared spontaneously. No serious or death -related case has been reported at this stage. The results are considered convincing enough for Unique to prepare an authorization request to the FDA for 2026, pending complete scientific publications.
Towards a new therapeutic and preventive era
AMT-1130 therapy thus opens a hitherto unexplored therapeutic path. His implications go beyond Huntington's disease. According to Professor David Rubinsztein (University of Cambridge), if this approach is confirmed, it could be adapted for other neurodegenerative pathologies. Let us quote Parkinson, certain forms of Alzheimer's or spinal muscular atrophy. We target the defective proteins specific to each disease.
But the researchers also envisage a preventive use of treatment in carriers of the mutated HTT gene. So even before the first symptoms appear during the stage, called “Huntington Zero”. It concerns genetically diagnosed, but clinically asymptomatic individuals. A first prevention test is in preparation, under the aegis of Sarah Tabrizi.
However, several obstacles remain. First, the cost of treatment will be high. Admittedly, the price is not yet fixed. But comparisons with other gene therapies (such as that of hemophilia B, billed 2.6 million euros per patient) suggest limited short -term access. Then, surgical complexity reduces the possibility of large -scale deployment without specialized training.
Finally, the test only carried on 29 patients, a still modest workforce. Phase IV studies post-marketing will be essential to verify the sustainability of the effects, long-term risks and broader and diverse population efficiency.
Despite these limits, the treatment represents a paradigm shift, by questioning the inevitability of a hitherto incurable disease. “” It's just a start, but it's a solid start “Concludes Tabrizi.
With an unwavering passion for local news, Christopher leads our editorial team with integrity and dedication. With over 20 years’ experience, he is the backbone of Wouldsayso, ensuring that we stay true to our mission to inform.
