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HTTRx, a treatment that generates high expectations in the Huntington community, significantly decreases the levels of the mutant protein that causes neuronal dysfunction and death in those affected by the disease. The results suggest that the treatment has a good safety profile.
One of the most prestigious scientific journals in the world, The New England Medical Journal (NEJM ), was the chosen way to publish the results of a phase 1-2a clinical trial in which the safety of IONIS-HTTRx, a therapy aimed at decrease huntingtin levels in patients with Huntington's disease.
People affected by the disease carry a genetic mutation that leads to a mutant and toxic protein, huntingtin, which eventually causes the death of neurons in certain areas of the brain.
As a result, patients experience symptoms such as abnormal movements and cognitive and psychiatric disorders.
The HTTRx therapy specifically aims to reduce huntingtin levels to prevent damage to the nervous system caused by the toxic form of the protein.
The results published in NEJM they are not unknown, since they've been widely circulated before. However, the publication provides access to more details about the clinical trial and, in a way, "formalizes" the results to the scientific community.
You may also be interested in reading: IONIS-HTTRx, Huntington's most anticipated drug, generates clinical improvements
HTTRx: decreases huntingtin levels with a good safety profile
At the trial they participated 46 patients in the initial phase of the disease. Of these, 34 received the treatment and 12 received a placebo (substance with no real effect on the body).
The therapy was administered intrathecally (in the spine, by a puncture) and each patient received 4 doses, one every four weeks. Patients were organized in groups with different increasing doses (10 mg, 30 mg, 60 mg, 90 mg or 120 mg).
Cerebrospinal fluid samples were collected to evaluate huntingtin and other variables before each injection, and then at the fourth and eighth weeks after the last dose.
It should be borne in mind that this is an initial phase clinical trial, The main goal is to evaluate if the treatment is safe before applying it to a larger number of patients in other phases of clinical trials.
To badess safety, instruments such as electrocardiograms, blood tests and psychological tests were used.
The researchers observed that adverse events they were very common and affected 98% of participants, but there was no significant difference in the number of adverse events between the group receiving the drug and the control group.
The above suggests that adverse events are not related to the drug itself, which argues for a good safety profile.
Adverse events in those who received HTTRx were mild or moderate, the most common pain being related to the procedure of administration or headaches due to puncture.
Cerebrospinal fluid badysis revealed a Clear reduction of mutant huntingtin and this reduction was dose-related, that is, the more absorbed the drug was, the higher the level of protein reduction.
Now, huntingtin levels decrease in the cerebrospinal fluid (which is supposed to be a reflection of what is happening in the brain), but Does this result in symptomatic improvement or slowing down of the patient's deterioration?
This is the most legitimate doubt for patients and their relatives, but we must remember that this is a trial whose main objective is to evaluate the safety of treatment. The number of patients and the duration of follow-up are not sufficient to draw conclusions about their effectiveness.
That said, it is true that some initial measures have been made in relation to the clinical progression of the disease. The results are interesting, but they must be taken with caution.
You might also be interested in reading: Update on Zolgensma, treatment in research on spinal muscular atrophy (AME) that could be published soon
Correlation between the decrease in huntingtin levels and the improvement of symptoms of the disease
During the trial, patients received a scale that evaluates the progression of the disease (called the Unified Huntington's Disease Evaluation Scale, cUHDRS). get a better score on this scale.
Positive result, but the researchers themselves call to "interpret this result with caution".
A clinical trial is already under way to decide on the marketing of the treatment.
Although the publication in NEJM corresponds to the results of a Phase I and IIa clinical trial (initial) now a pivotal Phase III trial is underwaythat is, a decisive study that regulators will take into account when deciding on the commercialization of therapy.
According to Scott Schobel, one of the leaders of the research project:
In conversations with regulators, EMA and the FDA, we made the decision to move directly to a pivotal study. Huntington's disease has serious unmet needs and Phase II would have cost at least another three to five years … "
This latest trial aims to recruit a total of 660 patients and will be developed in 46 sites around the world, including several places in Spain.
You might also be interested in reading: How to find a clinical trial? These sites help you find them
The sources
Anette Breindl (2019): Huntington's hopes present at AAN 2019. At http://www.bioworld.com/content/huntingtons-hopefuls-present-an 2019-0
Sarah J. Tabrizi et al. (2019): Target the expression of huntingtin in patients with Huntington's disease. The New England Medical Journal.
About the author
Dunia Chappotin
Psychologist, Master in Psychogerontology and founder of TiTi. If I do not write, I read. There is a third option: it can be lost somewhere because I am very distraught.
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