Patricia Inacio, PhD,  science writer—

Envisagenics has raised a total of $2.35 million to continue working to discover RNA-based therapies for diseases linked to RNA splicing errors, such as spinal muscular atrophy. The company uses an innovative platform that couples RNA splicing analysis with artificial intelligence. The biotechnology company's drug discovery platform, called SpliceCore, aims to develop therapeutics that correct splicing errors in RNA — the molecule that, along with DNA, gives the instructions to make all the proteins required for our cells to function. Errors in RNA splicing — a natural process cells use to generate a variety of RNA molecules by simply arranging the building blocks that compose the RNA molecule in different ways — are the cause of more than 300 genetic diseases, including SMA. With RNA splicing analysis, researchers are able to analyze millions of RNA sequence codings and identify RNA splicing errors. The most plausible and likely targets for treatments, after being validated in experiments using patients’ data, are then identified by artificial intelligence. With a target identified, researchers can then design a tailored drug and investigate its action, or how well it might work, using the SpliceCore's modular platform. The money was raised in what is called seed capital round, in which an investor funds a company in exchange for an equity stake in it.

Preimplantation genetic diagnosis may help couples prevent the risk of having a child with spinal muscular atrophy (SMA). The case report “The clinical application of preimplantation genetic diagnosis to prevent spinal muscular atrophy in a Chinese family: A case report” was published in the Journal of the Neurological…

Defects in our cells’ natural cleaning system — called autophagy — may be a trigger for the development of motor neuron diseases such as spinal muscular atrophy (SMA), researchers at the University of Würzburg, Germany, suggest. Their study, “Plekhg5-regulated autophagy of synaptic vesicles reveals a pathogenic mechanism in motoneuron…

Invitae presented data that supports combining genetic sequencing with platforms that detect copy number variant (CNV) as a way of diagnosing neuromuscular disorders — such as spinal muscular atrophy — and one superior to genetic sequencing alone. The results were in one of the 15 posters Invitae, a genetic information…

Human urine cells grown in a lab could help scientists test spinal muscular atrophy treatments, a Chinese study reports. The SMA patients from whom they were collected have a gene mutation associated with the disease, the researchers said. The study, “Application of urine cells in drug intervention for spinal muscular…

The gene therapy developer AveXis will start a pivotal clinical trial of AVXS-101 for people with SMA type 1. U.S. Food and Drug Administration officials agreed to the trial after AveXis submitted information the agency requested on the drug's manufacturing process and other matters. The request was made at a meeting the sides held in May. AveXis did not say in its announcement whether the pivotal trial would be a Phase 2 or Phase 3 study. The company has completed a Phase 1 trial of AVXS-101. Most pivotal trials are Phase 3, but occasionally they can be Phase 2. . AVXS-101 is a proprietary gene therapy for SMA types 1 and 2. Designed to deliver a functional copy of an SMN gene to motor neuron cells, it aims to prevent additional muscle degeneration. The pivotal trial in SMA type 1 – called STR1VE – will be an open-label, single-arm, single-dose, multi-center study. It will evaluate the safety and effectiveness of a one-time dose of AVXS-101 delivered intravenously or directly into the blood circulation. Researchers will administer a dose established in a Phase 1 trial that they confirmed with new analytical methods that the FDA reviewed. The dose was also extensively tested in a mouse model of SMA. AveXis expects to enroll in the trial at least 15 patients with SMA Type 1 younger than six months of age. One of the trial's primary objectives will be to see if AVXS-101 can help an 18-month-old infant sit without help for at least 30 seconds. Another primary objective will be to help an infant achieve event-free survival at 14 months of age, and to see whether AVXS-101 helps patients thrive — that is,  not requiring feeding support, tolerate thin liquids and maintain weight. Another secondary objective will be to help infants get off ventilator support at 18 months of age. Updates of these studies are expected at the end of the year.

Today is thursday, September 14. I'm Mike Nace, Executive Editor of SMA News today A cocktail of two microRNAs and two transcription factors is enough to transform human skin cells directly into motor neurons, scientists report — an achievement of potentially considerable importance in understanding such motor neuron diseases as spinal muscular atrophy. Damage to motor neurons underlies several devastating and paralyzing diseases, from SMA to ALS. Scientists have struggled to grow human motor neurons in the lab for research purposes, which is one reason this work is so notable. Researchers were able to convert skin cells from healthy adults into motor neurons. Importantly, this process also didn’t require skin cells to change into stem cells before becoming motor nerve cells. In the current study, the research team further investigated the role of these microRNAs and how they help convert skin cells into motor neurons. It found that the microRNAs identified in the study assist cells in holding at a stage where they are ready to convert to neurons. But they were inactive and need more help. After extensive research, researchers identified two transcription factors — ISL1 and LHX3 — were the missing link. Once added to the mix, skin cells turned into spinal cord motor neurons in about 30 days. The four factors — microRNA-9, microRNA-124, ISL1 and LHX3 — help cells shed their skin cell “genetic identity” and embrace instructions that lead them to becoming motor nerve cells, scientists said. The converted motor neurons showed a similar genetic profile — in terms of gene activation and how they work — to mouse motor neurons. How well their genetic profile compares to human motor neurons is still a question, because these cells are very difficult to obtain from living adults. Future studies will let researchers determine how well their converted motor neurons match natural human motor neurons.

Some discouraging news for the SMA community, as, according to the results of the CARNIVAL clinical trial, Valproic acid, also known as VPA, combined with L-carnitine does not improve the survival of SMA type I patients Previous studies suggested that VPA is a potential therapeutic candidate for SMA. In the CARNIVAL Type I trial, researchers led by Boston's Massachusetts General Hospital set out to investigate the safety and therapeutic potential of VPA, combined with L-carnitine, in infants with SMA. L-carnitine is a compound involved in cellular energy production. The Phase 2 study enrolled 37 infants with SMA type I aged two weeks to 12 months from seven clinics in the United States and Canada, and one in Germany. Cure SMA and Cure SMA Canada funded the study for the North American sites. Patients completed two screening visits within a two-week period to establish disease parameters at baseline. The babies then received two daily doses of L-carnitine and VPA. Researchers measured treatment effects at three and six months and compared them to an untreated, matched disease group of 57 type I infants. They chose controls retrospectively from a larger cohort of 151 SMA type I infants enrolled in the  University of Utah's Project Cure SMA database. The study's primary endpoint was to determine the treatment's safety and adverse effects. Secondary endpoints included survival, time to death or ventilator dependence, defined as more than 16 hours of ventilator support per day. Researchers detected 245 adverse effects, mostly related to respiratory problems, in 95 percent of patients. These resulted in 14 deaths. Overall, the CARNIVAL Type I trial proves no survival benefit for infants with SMA type I treated with L-carnitine/VPA.

Anthem recently issued an updated insurance policy, expanding its coverage for the use of Spinraza (nusinersen), the first approved treatment for spinal muscular atrophy (SMA). The update revises the criteria for Spinraza in the treatment of onset of SMA-associated signs and symptoms to children younger than 21 months old. The previous…

Several experts are wondering how best to determine which spinal muscular atrophy (SMA) patients will benefit most from treatment with Spinraza (nusinersen), due both to its high cost and growing demand. Dr. Claudia A. Chiriboga, a neurology and pediatrics professor at Columbia University Medical Center, said Spinraza must be given every…