A laboratory announces positive data on a drug based on gene editing to relieve outbreaks caused by hereditary angioedema, an inflammatory pathology that affects the skin, mucous membranes and the digestive system, among others
A therapy based on CRISPR technologythe gene editing tool, has shown good results in the treatment of hereditary angioedemaas announced by the company responsible for the therapy, Intellia Therapeutics. Six patients affected by the genetic disease, the company has underlined, have been able to relieve your symptoms thanks to this experimental treatment that specifically targets the genetic mutation that causes the disorder.
The results of the research have been presented at the 2022 Bradykinin Symposium in Berlin (Germany) -a congress related to the disease- and, for the moment, they have not been published in any scientific journal, so they have not been subjected to the usual peer review.
The hereditary angioedema is a rare disease that can be serious and produces recurrent outbreaks of swelling of some parts of the body, such as the skin, the gastrointestinal mucosa or the upper airway. The hereditary form is estimated to affect 1 in 10,000 50,000 inhabitants, as pointed out by the Spanish Association of Familial Angioedema due to C1 Inhibitor Deficiency (Aedaf).
In most cases, the disorder is due to a mutation in the chromosome 11 leading to an enzymatic deficiency of the inhibitory factor C1 of the complement system. As a consequence, swelling is produced at various locations through a biochemical mediator called bradykinin, produced by the uncontrolled action of a protein, the kallicerene.
First results in six patients
According to company data, the treatment, called NTLA-2002, was administered intravenously to six patients. Half received a dose of 25 mg, which was increased to 75 mg in the rest.
The treatment, according to the information presented, is directed to the liver, where it blocks the action of the gene responsible for the disease, which prevents the cascade that is toxic for those affected from taking place.
The preliminary results of this phase I study showed that in those patients who had received a dose of 25 mg, the levels of kallikren were reduced, after eight weeks, by 65%. The reduction continued at 16 weeks after administration of therapy.
In patients who received the 75 mg dose, the reduction reached, on average, 92% at eight weeks. At the time of the presentation of the study, there were no data on the evolution of this group of patients at 16 weeks.
In those nearly four months, disease flares were reduced by 91% in patients taking the 25-mg dose, the company said.
More data is scheduled to be presented at the American Society of Allergy, Asthma and Immunology meeting in November, the company said.
Pending publication of scientific data
We will have to wait for more data and for it to be published in a scientific journal published by peers to know the real scope of the therapy. First, the advanced results are preliminary data from a phase I studydesigned primarily to assess the safety of therapy.
In addition, it must be taken into account that this is an analysis carried out on a small sample of patients. To know the efficacy, it is necessary to carry out a trial with a larger number of participants.
More data on possible side effects is also needed. Intellia has reported that in some patients signs of liver damage were detected temporarily and then disappeared.
For Jose Maria Millnmember of the Spanish Association of Human Genetics (AEGH), although “a lot of progress is being made in research with CRISPR technology, it is still early to draw conclusions on the possible usefulness of this therapy in hereditary angioedema”.
the company Intellia Therapeutics also announced having achieved good results with the use of CRISPR technology in cases of transthyretin cardiac amyloidosis, a heart disease caused by abnormal extracellular protein deposition.
“Good results are being seen in monogenic diseases caused by the abnormal production of proteins that are toxic through the use of CRISPR to block the action of the gene that is not working correctly,” explains Milln.
Either way, “it’s a technology that’s still in its infancy. Much remains to be done and much progress needs to be made for this to reach the clinic.“, warns the specialist.
Gene editing results
This road is especially long for disorders where the genetic editing that has to be done is more complex than what is needed to, as in these cases, block the production of a toxic protein – for example, if what has to be done is to correct a letter of the genome and change it for another. “In these cases, the efficacy that research is showing today is low.”
“One of the problems today with CRISPR with what is called off targetsthe chance that by targeting a given mutation make other modifications in unwanted places“says the researcher.
The use of this gene editing tool is prohibited on embryos. In 2018, the Chinese scientist He Jiankui announced that he had created two genetically modified babies, the twins Lulu and Nana, a fact for which he was condemned.