LMI070 (branaplam, formerly known as NVS-SM1) is a potential treatment being developed by Novartis for newly diagnosed babies with type 1 spinal muscular atrophy (SMA).

How LMI070 works

SMA is caused by a mutation in a gene called survival motor neuron 1, or SMN1. The mutation leads to little or no SMN protein produced by this gene. SMN is an essential protein that maintains motor neurons or nerve cells that control the activity of healthy muscles.

Humans have a closely related gene, SMN2, frequently referred to as the SMA back-up gene.  It’s also able to produce SMN protein, but some versions of the protein produced by SMN2 aren’t fully formed, according to Novartis. 

LMI070 is designed to increase the amount of functional SMN protein produced by the SMN2 gene. 

LMI070 was first discovered by Novartis after about 1.4 million compounds that could increase the production of SMN protein were tested in a nerve cell model in the laboratory. After LMI070 was identified, it was tested in mice with SMA, and was found to produce greater amounts of SMN protein, leading to improvements in body weight and survival in SMA mice.

The selectivity of the drug-DNA interaction is found in a limited number of genes, reducing the chances of the drug interacting with other genes and causing severe side effects in humans. These positive preclinical results led to a Phase 1/2 trial.

LMI070 in clinical trials

The purpose of the Phase 1/2 study (NCT02268552) was to evaluate the safety, tolerability, pharmacology, and efficacy of LMI070 after 13 weeks of treatment, and to estimate the maximum tolerated dose and optimal dosing regimen in patients with type 1 SMA.

But in May 2016, Novartis had to pause enrollment for this study because animal studies conducted while the human trial was underway showed unexpected injuries to the peripheral nerves and spinal cord, testes, and blood vessels in the kidney.

On Sept. 20, 2017, Novartis released an update announcing the company is resuming enrollment for the trial in Europe, where different doses of LMI070 are being tested. They have also modified the trial design, giving participants a choice of a weekly oral treatment or a feeding tube.

Next steps for LMI070

An investigational new drug (IND) application was recently accepted by the U.S. Food and Drug Administration, which means that U.S. participants will also be allowed to participate in the study


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