Research Project
8057567
DESCRIPTION (provided by applicant): Multiple sclerosis (MS) is an inflammatory autoimmune disease in young adults, affecting more than 530,000 people in the United States and approximately 2 million worldwide. MS is characterized pathologically by inflammation, demyelination and axonal damage in the brain and spinal cord. In this disorder, the immune system mistakenly attacks the myelin sheath, which further damages surrounding nerves and eventually makes the patient wheelchair-bound. Current FDA-approved disease-modifying treatments for MS, e.g., beta interferon 1a (Avonex(r) and Rebif(r)) and 1b (Betaseron(r)), glatiramer acetate (Copaxone(r)), mitoxantrone (Novantrone(r)) and newly marketed Tysabri(r) specifically target the inflammatory phase of the disease and have no clear effect on myelin repair. That more than half of MS patients do not respond well to existing treatments may be due, in part, to their failure to address the reparative component. Therefore, restoration of damaged axons and their surrounding myelin sheath, namely neuroregeneration and remyelination, may be more important than simple relief of the acute inflammatory atack when one is focused on long-term functional recovery. Cognosci has innovatively created a neurorestorative strategy based on the apolipoprotein E receptor-binding domain that can mimic the major bioactivities of apoE holo-protein and can be potentially used for treatment of related neurological disorders like MS. We have identified a lead compound, COG112, using multiple animal models of human MS and have obtained proof-of- concept that the apoE-mimetic COG112 can properly attenuate inflammatory responses and facilitates myelin reconstruction, as well as axonal regeneration both in vitro and in vivo, indicating its potential utility for MS patients in the Clinic. To translate findings from lab bench to patient bedside, Cognosci will develop a clinically favorable dosing formulation that permits sustained release of the therapeutic compound. Successful development of a sustained release formulation will reduce the frequency of dosing and thus overcome the major limitation of frequent dosing typically needed for peptide therapeutics. The completion of the proposed studies is a critical step to validate this first-in-class remyelination therapy for MS in a more clinically favorable formulation that reduces the frequency of dosing. PUBLIC HEALTH RELEVANCE: Multiple Sclerosis is a devastating inflammatory autoimmune disease affecting half million young Americans. Uncontrolled progress of the disease usually put the victims on wheelchair for a life-ling time. Because MS is very complicated in etiology and pathology, the current MS drugs on the market only target on the inflammatory component of disease. Novel therapeutics is highly demanded. Cognosci has innovatively designed a compound, namely COG112, that had demonstrated multiple favorable properties for treatment of MS that can not only attenuate the inflammatory attack, but also stimulate the reconstruction of damaged myelin sheath as well as the reconnection of broken axons. The purpose of this proposal is to develop a sustained release formulation that permits extended release of therapeutic agent therefore reduces the need for frequent injection. This is a very important step from preclinical development towards clinical trials. Successful completion of this project will enable initiation of an IND safety/toxicity study to obtain FDA approval for clinical trial and is requisite for eventually bringing to clinic.
