Indoline Compounds for the Treatment of Spinal Muscular Atrophy (SMA) and Other Diseases
Description of Invention:
With the goal to treat SMA in patients, several indoline compounds were made and tested for activity. Tests in cells demonstrate that these drugs increased the levels of active SMN protein. This is encouraging since low levels of this protein appears to be the cause of neuronal death that leads to SMA. This class of compounds appears to operate via read-through of a non-sense stop-codon to produce full length, functional protein in SMA models. This mechanism may have utility in several other neurological disorders, including cystic fibrosis and Duchene’s Muscular Dystrophy.
In addition, these compounds have also been shown to increase the concentration of a glutamate transporter protein in cells, which acts to recover glutamate back into neurons after release. Since the toxic effect of unrecovered excess glutamate is observed in many notorious neurological conditions, these compounds have potential for prevention or treatment.
Applications:
Treatment of SMA in infants and children
Treat genetic-based diseases that result from a premature stop of protein synthesis such as muscular dystrophy and cystic fibrosis
Treating or preventing neurological diseases presenting glutamate toxicity like multiple sclerosis, Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis (ALS), or others
Market:
SMA is a rare genetic disease estimated to affect 1 in 6,000 births and leading genetic cause of death in infants and toddlers.
Over 25,000 Americans are believed to suffer from SMA and the market size has been estimated between $250 million and $750 million.
Development Status:
Pre-clinical, Toxicology and Safety Studies, Animal Models (Dogs and Primates)
Relevant Publication: MR Lunn, DE Root, AM Martino, SP Flaherty, BP Kelley, DD Coovert, AH Burghes, NT Man, GE Morris, J Zhou, EJ Androphy, CJ Sumner, BR Stockwell. Indoprofen upregulates the survival motor neuron protein through a cyclooxygenase-independent mechanism. Chem Biol. 2004 Nov;11(11):1489-1493. [PubMed abs]
Licensing Status: Available for exclusive or non-exclusive licensing.
Collaborative Research Opportunity:
The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize drugs for the treatment of SMA, as well as investigation into novel uses for these indoline compounds. Please contact Dr. Melissa Maderia at maderiam@mail.nih.gov or 301-451-3943 for more information.
Portfolios: Internal Medicine Central Nervous System
Central Nervous System -Therapeutics-Neurological Therapeutics-Alzheimer Central Nervous System -Therapeutics Internal Medicine-Therapeutics
For Additional Information Please Contact: Norbert J. Pontzer PhD JD
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5502
Email: pontzern@mail.nih.gov
Fax: (301) 402-0220
