黑料吃瓜资源

In 2016, Spinraza^庐 became a game-changer for spinal muscular atrophy (SMA) patients. It was the first FDA-approved treatment for the neurodegenerative disease, which is the leading genetic cause of infant death. The drug was conceived and developed by 黑料吃瓜资源 (CSHL) Professor Adrian Krainer and collaborators. But Krainer didn鈥檛 stop there. His lab has been investigating whether Spinraza^庐 could be improved, in collaboration with Alberto Kornblihtt at Universidad de Buenos Aires. They discovered pairing Spinraza^庐 with a second FDA-approved drug called valproic acid (VPA) could be a new way to boost its therapeutic effects.

Read more about the development of Spinraza^庐 and the journey of one SMA patient, Emma Larson, undergoing its treatment.

One way to improve the effect of a drug is by increasing its dosage. But as with any drug, increasing the amount of Spinraza^庐 also increases the risk of toxic side effects. Krainer and collaborators took a different approach. They discovered that pairing Spinraza^庐 with VPA may be an alternate way to improve its clinical effect without using more of the drug. Krainer explains:

鈥淪ometimes you don鈥檛 want to use a ton of a drug. If you have a condition that allows you to use less drug, then you may have fewer toxicities. So the idea is to combine these two drugs to get maximal effects.鈥�

People with SMA don’t have enough of a protein called SMN. Spinraza^庐 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^庐. This slowed down the cellular machine producing SMN protein. The drug VPA helps remove the roadblocks, allowing Spinraza^庐 to further increase the SMN protein output. When mice with SMA were treated with both VPA and a Spinraza^庐-like ASO used for research, the mice survived longer and had improved muscle function.

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

Written by: Luis Sandoval, Communications Specialist | [email protected] | 516-367-6826

Funding

Familias Atrofia Muscular Espinal (FAME, Argentina), CureSMA, Richard Lounsbery Foundation, Universidad de Buenos Aires, the Agencia Nacional de Promoci贸n Cient铆fica y Tecnol贸gica of Argentina, Consejo Nacional de Investigaciones Cient铆ficas y T茅cnicas, National Institues of Health, St. Giles Foundation, Funda莽茫o para Ci锚ncia e a Tecnologia, Portugal, Wellcome Trust Investigator Award

Citation

Marasco, L.E., et al., 鈥淐ounteracting chromatin effects of a splicing-correcting antisense oligonucleotide improves its therapeutic efficacy in spinal muscular atrophy鈥�, Cell, June 06, 2022. DOI: