New ALS impact from ImStar

ImStar’s lead candidate derived from withaferin A targets TANA inflammation pathway

Kelsey Kaustinen
VANCOUVER, British Columbia—Biotechnology company ImStar Therapeutics has announced the selection of IMS-088 as its lead drug candidate for treating amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. In connection with this move, the company has also filed a patent application with the United States Patent and Trademark Office covering novel withanolide therapeutics.
 
At present, no effective treatments are available for this disease, says Daniel Wattier, CEO of ImStar. The only drug approved for the treatment of ALS, Rilutek, was approved in 1995.
 
“The experience of Rilutek is that it may extend survival by up to three months—at least, that was what was demonstrated in a clinical trial,” explains Wattier. “However, experience shows it really has very minimal impact on the disease and it has some side effects. They’re not atrocious, but they’re meaningful enough that it’s not the greatest drug to take. So this is a disease area where new treatments that go after the underlying mechanism of disease are just vitally needed.”
 
That’s where ImStar’s IMS-088 comes in. The compound is the result of a discovery by Dr. Jean-Pierre Julien, co-founder and chief scientific officer at ImStar, of a new target for ALS: TDP-43 associated NF-kB activation (TANA). TAR DNA-binding protein 43 (TDP-43) was recently identified as the primary disease-associated protein in ALS. While the protein normally regulates gene expression and is found in the nucleus of cells, it is misprocessed in ALS-affected cells and collects in the cytoplasm instead, leading to motor function loss. Julien discovered that TDP-43 associates with and activates nuclear factor-kB, an inflammation-regulating protein, in patients with ALS.
 
IMS-088 is derived from withaferin A, a compound isolated from the leaves of the winter cherry plant, Withania somnifera. Withaferin A has been shown to inhibit the activation of the TANA pathway, providing improvements in function and extended survival in preclinical mouse disease models, and IMS-088 is a modified version of the compound—a withanolide—that has demonstrated superior drug-like properties, safety and potency in preclinical studies.
 
Targeting this pathway is thought to have potential in treating other neurodegenerative diseases as well, as Wattier notes that TDP-43 proteinopathy “is implicated in a number of other neurodegenerative diseases.” One such disease is frontotemporal dementia, which he says has been found to share several pathological similarities with ALS. Both Alzheimer’s disease and Parkinson’s disease express TDP-43 pathology as well.
 
Wattier says ImStar is currently performing validation studies of IMS-088 in two disease models of ALS, and once those are complete—the company is aiming to be done with them in the second half of 2014—IND-enabling studies will begin. They are about 12 to 18 months from starting a clinical trial, says Wattier.
 
ALS is an indication with significant opportunity for growth, says Wattier, noting that the condition would qualify as an orphan disease with the U.S. Food and Drug Administration and “allow for an orphan development pathway.” In addition, he says the need is so high “that we feel any drug that has the capacity to even improve the disease in a minor way would find a welcome market.”
 
“We are very excited to announce the selection of IMS-088 as ImStar’s lead ALS compound. As we continue with preclinical development [in 2014], we hope to establish IMS-088 as a safe and effective new drug candidate for ALS,” said Julien.
 
ALS is a progressive neurodegenerative disease that targets the motor neurons in the brain and spinal cord responsible for controlling voluntary muscle movement. As these nerve cells are degraded, quality of life deteriorates and affected individuals eventually face paralysis. The disease has a mortality rate of 50 percent at 18 months, and most patients die within two to five years after initial diagnosis. Approximately 3,000 people suffer from ALS in Canada, with some 30,000 afflicted in the United States.

Kelsey Kaustinen

Subscribe to Newsletter
Subscribe to our eNewsletters

Stay connected with all of the latest from Drug Discovery News.

February 2023 Front Cover

Latest Issue  

• Volume 19 • Issue 2 • February 2023

February 2023

February 2023 Issue