Methods and Compositions for the Diagnosis and Treatment of Central Nervous System Autoimmune Diseases
Multiple sclerosis (MS) is the most common disabling neurological condition of young adults around the world. According to the estimation by the Multiple Sclerosis Foundation, there are more than 400,000 people in the United States and about 2.5 million people worldwide that have MS. About 200 new cases are diagnosed each week in the United States. MS is highly heterogeneous: there is no single treatment that works for all patients. Interferon beta (IFNβ) is the conventional first-line treatment for MS, but it is not effective for a significant proportion (7-49%) of MS patients. Unfortunately, these patients may miss the proper treatment window and progress to a stage of irreversible neuronal damage. Methods to distinguish and treat IFNβ-resistant MS patients are thus needed.
The inventors have discovered Ltbr, CXCR2, CXCR1, and/or Sema6B as biomarkers that can diagnose MS patients insensitive to conventional IFNβ treatment. It has been shown that these targets are highly elevated in IFNβ-tolerant animal models. Such diagnosis can provide guidance on treating MS patients and possibly save valuable time and money on an ineffective treatment. In addition, these biomarkers are, potentially, novel theraputic targets for treating IFNβ-tolerant patients. Inhibition of even one of these targets can lead to the rescue of neuronal damage (see figure)
This techonolgy can potentially be used for other central nervous system autoimmune diseases including, but are not limited to, myasthenia gravis, Guillian-Barre syndrome, transverse myelitis, and chronic inflammatory demyelinating polyneuropathy.
- Technology can diagnose IFNβ-tolerant MS patients
- Animal models are highly predictive
- Concept proven with patient samples
- Unique therapeutic targets that are distinct from currently marketed medications
- Multiple targets can be combined to develop personalized treatment plan
Duke File (IDF) Number
- Shinohara, Mari
- Inoue, Makoto
- Inoue M et al. (2016) An interferon-beta-resistant and NLRP3 inflammasome-independent subtype of EAE with neuronal damage. Nat Neurosci 19:1599–1609.
For more information please contact
- Gopalakrishnan, Karthik