A genical therapy that targets the accumulations of a protein in the brain has managed to slow down the progression of Huntington’s disease.
Experimental gene therapy managed to slow down the progression of Huntington’s disease for the first time, a rare, hereditary and degenerative neurological disease. Although the study, on a very reduced number of patients, has not yet been published in a scientific journal, the preliminary results of a clinical trial, anticipated in a press release, show a 75% reduction in the speed of progress of the symptoms in 3 years.
Huntington disease: symptoms and causes
Huntington’s disease is a hereditary disease with a debut typically between 30 and 50 years of age that affects about 6-7000 people in Italy. It takes its name from the American doctor who first described it, in 1872 and is characterized by initial symptoms such as irritability, mood and motor coordination disorders, with movements similar to shots, random and uncontrolled, called “Korea”. When the disease progresses, Korea and cognitive disorders (as a loss of memory and difficulty in manifesting or recognizing emotions) worsen, and muscle control decreases, with difficulty talking, chewing and swallowing. The disease has a fatal course in general in 15-20 years.
Huntington’s disease is linked to a mutation of the HTT gene, which codes for a vital protein for the health of neurons, the huntin. The mutation does not disable the protein, but causes a toxic form to be produced, which forms sticky accumulations within the neurons, ending up destroying them. Just inherit one copy of the defective gene to develop the disease.
Micro molecules against mutant proteins
The experimental gene therapy developed by the Dutch pharmaceutical biotechnology company UNIQURE is called AMT-130 and aimed at anomalous and neurotoxic proteins, of which it slows down production. Through a harmless virus, a pack of genetic material is delivered to the brain that tells cells to produce a molecular “stop” signal called microrn. This micro filament has the task of deactivating instructions for the production of toxic protein.
The treatment is disbursed through a catheter directly in the brain of patients and in the two deep regions most affected by Huntington’s disease, the caudate nucleus and the Putamen: the intervention can request from 12 to 18 hours because doctors must use real -time brain scans to drive the catheter, but a single injection of the drug seems sufficient. In the past, an analogous attempt to block the production of Diffettosa Huntingina passing through the cerebrospinal liquid, with a slightly less invasive procedure, had failed, perhaps because the RNA had been too diluted or eliminated by the action of enzymes.
Slowdown progression
In the clinical study 29 people were enrolled with advanced Huntington disease symptoms who received a more or less high dosage of the drug. The progression of their symptoms was compared with that observed in almost 1,600 unused patients and in a stage of similar disease.
The 12 patients treated with the high dose, during the following three years, had a slowdown of about 75% in the progression of the disease: it means that the cognitive and motor drops that would normally be observed in one year have occurred on average over four years, as explained to BBC Sarah Tabrizi, director of the Huntington disease center of the University College London, who defined the “spectacular” results.
Prospective
None of the patients involved has been identified, but the BBC It says that one is a professional in the medical field who managed to return to work and that others still manage to walk, in a stage of the disease in which they would otherwise use a wheelchair.
The treatment, which for the moment does not seem to cause noteworthy side effects, still has some limits: it must be administered with an invasive surgical procedure and will probably be very expensive (the prices of some gene therapies reach 2 million dollars, 1.7 million euros, or more). In addition, the levels of neurofilaments (proteins present in the scaffolding of neurons) in the cerebrospinal liquid of patients, albeit decreased, suggested that these people were still losing neurons because of the disease, albeit more slowly.
It will be necessary to wait for the scientific publication of the study for more information. Meanwhile, the company has communicated that it plans to submit an application for approval to the US food and Drug Administration at the beginning of 2026 and that the treatment could be available in 2027.
Taking targeting toxic proteins, the therapy, suitably modified, could also find research applications against other neurodegenerative diseases, such as Parkinson’s or Alzheimer’s.
