Candidate Drug Provides Benefit in Spinal Muscular Atrophy Mouse Models

PhD reports on a pharmacological characterization of the drug RG3039, demonstrates that it can extend survival and improve function in two spinal muscular atrophy (SMA) mouse models.

It appeared in a new publication in Human Molecular Genetics, the laboratory of Christine DiDonato. They have determined the minimum effective dose and drug action, thus contributing to dose selection and exposure estimates for the first studies with RG3039 in humans. As in cellular assays, the animal studies have shown that drug treatment leads to improvement in nuclear gem/Cajal body numbers in motor neurons. Gem loss is a cellular hallmark of fibroblasts derived from SMA patients; gem numbers inversely correlate with SMA disease severity.

Bad Drug Reactions can be Detected by Data Mining Electronic Medical Records
Electronic medical records can validate previously reported adverse drug reactions and report new ones, according to a new study by NJIT Assistant Professor Mei Liu.

In addition, the laboratory has shown improved functional outcomes, including treadmill walking and gait dynamics, in animals receiving the drug. The laboratory has been testing RG3039 in SMA mouse models with disease phenotypes ranging from mild to severe.The collective results suggest that RG3039 positively modifies motor unit pathologies and dysfunction, and that it may have therapeutic benefit for SMA.Spinal muscular atrophy (SMA) is a devastating hereditary disease that is a leading cause of infant and early childhood mortality.

Motor neurons in the spinal cord are affected, resulting in muscle weakness and in many cases breathing problems. SMA is caused by insufficient levels of the survival motor neuron (SMN) protein; depending on the level of SMN protein, patients may have mild to severe forms of SMA. There is currently no cure for the disease.The goal of early SMA drug discovery programs has been to identify small molecules that induce the SMN gene to produce sufficient levels of protein to improve motor neuron functioning in affected patients.

A promising drug candidate is RG3039, which has been shown to increase nuclear gem/Cajal body numbers in cellular assays.Says DiDonato: "We are very happy that our research was able to assist in the pharmacological characterization of RG3039 and contribute to dose selection and exposure estimates for the first studies with RG3039 in human subjects. We are indebted to my colleague, Nancy Kuntz, MD, and co-author laboratories of Drs. Jasbir Singh and Mike Kiledjian along with Repligen and Families of Spinal Muscular Atrophy (FSMA), who initiated the development of this drug candidate.

Neurodegenerative Disease may be Treated by Diabetes Drug
New research suggests that a drug used to control Type II diabetes can help repair the spinal cords of mice suffering from the inherited disease adrenoleukodystrophy.

The depth of our manuscript would not have been possible without this group collaboration. Also, it is reassuring that our results of improved motor unit dysfunction in SMA mice treated with RG3039 mirror the independent findings by the laboratories of Drs. Sumner and Ko. Improved neuromuscular function is an obvious goal for SMA therapies. Thus, this drug candidate warrants further investigation. Overall, this SMA candidate drugis an exciting time as we take another step forward towards developing therapies for SMA patients."

Source-Eurekalert

Trending as New Bath Salt Drugs Are 'Designer Stimulants'
A new drug problem in so-called bath salts -actually designer stimulants, packaged and sold in ways that skirt drug laws have emerged in the last few years.

Dutch City Flouts Drug Ban Leading to Coffee Shop Chaos
After cannabis cafes staged an open revolt by selling marijuana to foreigners, authorities in the Dutch drug tourism hub of Maastricht are hitting back on a war footing.