Argentine scientists successfully tested a treatment for Spinal Muscular Atrophy

Argentine scientists successfully tested a treatment for Spinal Muscular Atrophy

Argentine scientists successfully test a treatment for Spinal Muscular Atrophy


A team of Argentine scientists managed to successfully test a new treatment for Spinal Muscular Atrophy (SMA) in mice that optimizes one of the most widely used drugs by combining it with another existing drug, according to the Ministry of Science and Technology. Technology and the prestigious Cell magazine that brought the news to the front page.

The research led by Conicet scientists showed in “in vitro and in vivo tests” that the results of treatment with the drug “Nusinersen” – an antisense oligonucleotide (ASO) – can be improved if it is administered together with valproic acid, a drug currently used to treat cases of epilepsy.

Photo: Victoria Egurza

“We are working on a (cellular) phenomenon called ‘alternative splicing’ which means that each gene can code for more than one protein and SMA is a hereditary disease that alters this mechanism“producing insufficient amounts of the SMN protein, the molecular biologist and director of the research project, Alberto Kornblihtt, told Télam

Photo Victoria Egurza
Photo: Victoria Egurza

“The Uruguayan Adrián Krainer has already designed a therapy that corrects this defect and greatly improves the condition of patients. We investigated the mechanism in depth and discovered that another drug, called valproic acid, can be added, which allows the drug to be more efficient” , he added.

Alberto Kornblihtt Vanina Snchez and Luciano Marasco Press photo CONICET
Alberto Kornblihtt, Vanina Sánchez and Luciano Marasco / CONICET press photo.

The finding was announced at a press conference in the auditorium of the center where the research was carried out -the Institute of Physiology, Molecular Biology and Neurosciences (Ifibyne) of the UBA and Conicet-; a meeting that was also attended by the Minister of Science and Technology Daniel Filmus, the president of the Conicet Ana Franchi and the president of AME Families, Vanina Sánchez.

Research led by Alberto Kornblihtt on therapies against SMA is the cover of the journal Cell


What is spinal muscular atrophy?

Spinal muscular atrophy (SMA) is a rare neurodegenerative disease that affects motor neurons and is caused by mutations in both copies of the SMN1 gene.

Although there are different types of SMA, determined by the severity of the disease and the time of onset of symptoms, this disease is characterized by a progressive loss of muscle strength and can affect the ability to speak, walk, swallow and even breathe .

Until the end of 2016, the treatments available for SMA were only supportive, and there was no pharmacological therapy that could stop or slow the progression of the disease.

Alberto Kornblihtt and Luciano Marasco Press photo CONICET
Alberto Kornblihtt and Luciano Marasco / CONICET press photo.

This situation changed when in December of that year the United States Food and Drug Administration (FDA) authorized the use of a drug known as Nusinersen, which was later also approved in Argentina.

This drug makes it possible to increase the production of the SMN protein in patients with SMA and thus stop or slow down the progressive death of motor neurons.

“Our results were obtained in human cells in culture and in mice model of the disease, but the effectiveness in patients still needs to be tested and for that it will be necessary to carry out clinical trials with great rigor,” he said.

The molecular biologist and researcher at Conicet explained that the finding of this “new mechanism” was “based on our basic investigations of more than 25 years” and the expectation is that “it will allow the design of a more efficient combined therapy for the disease.”

SMA mice given Nusinersen in combination with a histone deacetylase inhibitor, such as valproic acid, have longer survival, gain more weight, and have better motor properties and greater forelimb strength than mice. mice to which only Kreinen’s drug is administered”, pointed out Luciano Marasco, doctoral fellow of the Conicet at Ifibyne and first author of the work.

Both stressed that this research began as a result of a direct demand from the Spinal Muscular Atrophy Families Association (FAME), whose representatives literally “knocked on the door of our office” one day to ask them to focus their research work on the development of new and better treatments to treat the illness suffered by their children or other family members.

“We are committed to research in basic science because we understand that the more that is known about the subject, the more likely it is that better therapies will be developed,” says Vanina Sánchez, president of FAME Argentina (see box).

And, according to Kornblihtt, it was thanks “to his demand, his request, his wisdom” that the results presented today were reached.

“In order for research groups to dedicate themselves to this type of task, in addition to state promotion, there must be a demand, whether from the private production system, the state sector, or family members,” he added.

Alberto Kornblihtt Press photo CONICET
Alberto Kornblihtt / CONICET press photo.

For his part, the Minister of Science, Technology and Innovation Daniel Filmus described the result of this research as “an Argentine pride” and highlighted “two fundamental qualities” of the science-society relationship.

“One is the talent of its researchers when the State generates the conditions to be able to develop them and the second is the demand capacity, -even direct- of our civil society that not all countries have”said.

In her turn, the president of the Conicet Ana Franchi pondered the “virtuous union between research groups, the present State, families, society” behind this scientific result, to which “companies that are going to be able to scale the Results of the investigation”

“The pandemic showed that we can respond to the immense needs of society and if we take into account that only 5% of rare diseases have a pharmacological response, the work ahead is enormous. It seems that a peripheral country with a complicated economy does not I could answer, but here it was possible and we believe that they will continue to be able to,” he said.

The researchers also tried combining ASO with another histone deacetylase inhibitor, such as trichostatin, with similar results, but unlike trichostatin, valproic acid is already approved for clinical use.

Families of spinal muscular atrophy patients now await clinical trials

The president of the Association of Spinal Muscular Atrophy Families (FAME), Vanina Sánchez, assured that now the “expectation” of the community is that “clinical trials can be carried out in Argentina to improve existing treatments” for this degenerative neuromuscular disease, after the good results obtained for a combined therapy at the preclinical level.

The Ministry of Science, Technology and Innovation and the Conicet announced today that a team of Argentine scientists managed to successfully test a new treatment for Spinal Muscular Atrophy (SMA) in mice that optimizes one of the most used drugs from combination with another existing drug.

“We have the expectation that this new step will open the door to clinical protocols, so that these combined treatments can be tested in people with SMA,” said Sánchez, whose son Joaquín (9) suffers from type 2 SMA.

Spinal muscular atrophy (SMA) is a rare genetic neurodegenerative disease – occurs in one every 10,000 live births – that affects motor neurons and is characterized by a progressive loss of muscle strength and can affect the ability to speak, walking, swallowing and even breathing.

“Joaquín was diagnosed at 15 months when he had to start walking. In fact, we arrived at the diagnosis because he was trying to stand up and take steps and he couldn’t, he fell,” he said.

“And after a few months we did a genetic study that determined that he had EMA, a disease for which at that time there was no (pharmacological) treatment available, although many other things were available, therapies so that the patient gets worse as slowly as possible, like kinesiology,” he said.

The boy attended the press conference where the results of the preclinical study were announced in a postural chair commanded by himself, although “he has periods of the day when he stands or takes steps with a walker.”

And all thanks to the treatment started when he was four years old with one of the available drugs because “what the natural history of the disease says is that without treatment a child with type 2 SMA cannot stand or walk.”

Sánchez explained that there are three pharmacological treatments available in the world, two of which have already been approved in Argentina and are being used, although they are not contemplated in the PMO but in a reimbursement policy.

“The first drug approved by the FDA in 2016 and by Argentina two and a half years later is called Nusinersen and its trade name is Spinraza. The second is Zolgensma, which is a gene therapy that replaces the defective gene approved in 2020 in the US and in January 2021 in our country, but there are still few patients in treatment because coverage guidelines are lacking,” said

The head of FAME added that “a third treatment approved in the world in 2020, which is Evrysdi – whose trade name is Risdiplan is the trade name – which is not yet approved in our country, but is in the process of being approved.”

As a consequence of this situation, Sánchez explained that “we have 50% of our population in treatment and the other 50% struggling to achieve it.”

“And on the other hand, combinations of pharmacological treatments are being tested and there are currently more than 20 lines of research that are betting on demonstrating that these combined treatments have an effect, especially in patients who have had the disease for a longer time and, therefore, , more deterioration”.

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