Prescription Medicine Tablets Concept

Una nueva y prometedora combinación de fármacos podría mejorar el tratamiento de la atrofia muscular espinal


El estudio encontró que combinar Spinraza® con ácido valproico podría potenciar sus efectos.

Un nuevo dúo de drogas

Spinraza® cambió el juego para las personas con atrofia muscular espinal (AME) en 2016. Fue el primer medicamento para la afección neurodegenerativa que es la principal causa genética de mortalidad infantil en obtener la aprobación de la FDA. Cold Spring Harbor Laboratory (CSHL), el profesor Adrian Krainer y sus colegas conceptualizaron y desarrollaron el medicamento.

Sin embargo, Krainer no se detuvo allí. Junto con Alberto Kornblihtt de la Universidad de Buenos Aires, su laboratorio ha estado investigando si Spinraza® podría mejorarse. Identificaron una estrategia novedosa para mejorar los beneficios terapéuticos de Spinraza® combinándolo con valproico[{” attribute=””>acid (VPA), a separate FDA-approved drug.

Increasing a drug’s dose is one method for increasing its impact. But like with any drug, using more Spinraza® puts you at risk for negative side effects. Krainer and his associates used a different strategy. They found that combining Spinraza® with VPA could be an alternative method for increasing its clinical effect without using more of the drug. Krainer explains:

“Sometimes you don’t want to use a ton of a drug. If you have a condition that allows you to use less of the drug, then you may have fewer toxicities. So the idea is to combine these two drugs to get maximal effects.”

People with SMA don’t have enough of a protein called SMN. Spinraza® is a type of molecule called an antisense oligonucleotide (ASO) that helps cells make more SMN protein from a gene called SMN2. The team discovered that there were roadblocks on the SMN2 gene when using Spinraza®. This slowed down the cellular machine producing SMN protein. The drug VPA helps remove the roadblocks, allowing Spinraza® to further increase the SMN protein output. When mice with SMA were treated with both VPA and a Spinraza®-like ASO used for research, the mice survived longer and had improved muscle function.

Over 11,000 SMA patients have been treated with Spinraza® in more than 50 countries. Krainer’s latest research shows that there’s always room for improvement. He hopes the team’s findings will help optimize the efficacy of Spinraza® treatments. He also hopes their work will help researchers who are trying to develop therapies for other neurodegenerative diseases.

Reference: “Counteracting chromatin effects of a splicing-correcting antisense oligonucleotide improves its therapeutic efficacy in spinal muscular atrophy” by Luciano E. Marasco, Gwendal Dujardin, Rui Sousa-Luís, Ying Hsiu Liu, Jose N. Stigliano, Tomoki Nomakuchi, Nick J. Proudfoot, Adrian R. Krainer and Alberto R. Kornblihtt, 9 June 2022, Cell.
DOI: 10.1016/j.cell.2022.04.031

The study was funded by Familias Atrofia Muscular Espinal, CureSMA, Richard Lounsbery Foundation, Universidad de Buenos Aires, Agencia Nacional de Promoción Científica y Tecnológica of Argentina, NIH/National Institutes of Health, Consejo Nacional de Investigaciones Científicas y Técnicas, St. Giles Foundation, Fundação para Ciência e a Tecnologia.

Deja un comentario

Tu dirección de correo electrónico no será publicada.