Sunday , August 1 2021

Antisense Therapy vs. Huntington: The results of the first clinical trial are published in which it is possible to reduce levels of toxic proteins

HTTRx, a therapy that generates great expectations in the Huntington community, significantly reduces the levels of mutant protein that causes neuronal dysfunction and death in those affected by the disease. The results show that the therapy has a good security profile.

One of the most prestigious scientific journals in the world, The New England Journal of Medicine (NO ), a means for publishing the results of Phase 1-2a is examined in which the safety of IONIS-HTTRx, a targeted therapy decrease the level of huntingtin in patients with Huntington's disease.

People affected by the disease are carriers of a genetic mutation that leads to a mutated and toxic form of a protein, a hunt that ends up causing death of neurons in certain parts of the brain.

The result is that patients manifest symptoms such as abnormal movements and cognitive and psychiatric disorders.

HTTRx therapy requires precisely lowering hortington levels to avoid damage to the nervous system caused by the toxic form of the protein.

Results published in NO they are not unknown, because they were widely published before. However, the publication gives access to more details about the clinical trial and in some way "makes official" the results to the scientific community.

You may also be interested in reading: IONIS-HTTRx, the most anticipated Huntington remedy, generates clinical improvements

HTTRx: Reduces hunter levels with a good security profile

They participated in the trial 46 patients at the initial stage of the disease. Of these, 34 received treatment, and 12 were given placebo (a substance without a real effect on the body).

Therapy was administered intrathecally (in the & quot; spine, via puncture) and each patient received 4 doses, one every four weeks. Patients were organized in groups with different growing doses (10 mg, 30 mg, 60 mg, 90 mg or 120 mg).

Cerebrospinal fluid samples were taken to assess hunting levels and other variables before each injection, and then on the fourth and eighth weeks after giving the last dose.

It must be considered that this is a clinical trial at the initial stage, the primary goal is to assess whether the therapy is safe before being administered to a larger number of patients at other stages of the clinical trial.

Instruments used such as electrocardiograms, blood tests and psychological tests were used to assess safety.

The researchers observed it unwanted events they were very common, affecting 98% of participants, but there were no significant differences in the number of adverse events between the drug group and the control group.

The above suggests that unwanted events are not related to the drug itself, which speaks in favor of a good security profile.

Side effects of those who received them HTTRx were mild or moderate, the most common pain was related to the administration procedure or headache due to puncture.

The cerebrospinal fluid analysis is reflected Clearly reduce the level of mutant hunters and this decrease was dependent on the dose, ie the greater the dose of the drug, the higher the level of protein reduction.

Now, the levels of Huntington fall into the cerebrospinal fluid (which should reflect what happens in the brain), but, Does this turn into symptomatic improvements or slows down the deterioration of the patient?

It is the most legitimate suspicion of patients and relatives, but we must remember that this is an essay whose primary goal is to evaluate the safety of treatment. The number of patients and the next time are not enough to reach conclusions about their effectiveness.

Thus, it is true that some initial measures were carried out in conjunction with the clinical progression of the disease. The results are interesting, but they should be taken with caution.

You may also be interested in reading: Update of Zolgensma, therapy in spinal muscular atrophy research (AME) that could be published soon

Correlation between the reduction in hunting levels and the improvement of symptoms of the disease


During the trial, patients were given a scale that assessed the progression of the disease (called the Unified Huntington Disease Scale, cUHDRS), and it was observed that patients experiencing a significant reduction in toxic proteins also had a tendency to get a better result that scale.

A reliable result, but that the researchers themselves call it "to interpret this result with caution."

A clinical trial is underway to decide on the commercialization of the therapy

Although posting in NO corresponds to the results of Phase I and IIa (initial) clinical trial now Phase III phase is underway, that is, a decisive study that regulators will consider to decide on the marketing of the therapy.

According to Scott Shebel, one of the leaders of the research project:

In discussions with regulators, both EMA and FDA, we decided to go directly to a key study. Huntington's disease has serious unsatisfied needs, and the second phase would cost at least three to five years … ".

This last trial attempts to hire a total of 660 patients and will be developed in 46 locations around the world, including several locations in Spain.

You may also be interested in reading: How to find a clinical trial? These websites help you find them


Anette Breindl (2019): Huntington's hopes are present in AAN 2019. At

Sarah J. Tabrizi et al. (2019): Direction of Huntington Expression in Huntington's Disease. The New England Journal of Medicine.

About the author


Dunia Chappotin

Psychologist, Master of Psychology and TiTi founder. If I do not write, I read. There is a third option: it can be lost somewhere, because I am very unreasonable.

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