This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disease of the central nervous system (CNS) in humans. Onset typically occurs between ages 20 and 40, thus making MS the leading cause of atraumatic neurological disability in young adults. Approximately 300,000 (0.1%) individuals in the United States have been diagnosed with MS. Inflammatory demyelinating lesions in MS can occur throughout the CNS, accounting for the variety of neurological signs and symptoms that may develop in individual patients. Frequently, MS patients present with a clinically isolated syndrome (CIS) with only one set of neurological presentation suggestive of MS. The presence of MRI lesions in patients with CIS has been highly predictive of a future diagnosis of MS. More than 85% of patients with MS initially experience a relapsing-remitting (RR) course with clinical exacerbations of neurological symptoms, followed by recovery that may or may not be complete. Although 10% to 20% of patients with MS have a 'benign' form, 50% of the patients develop a significant limitation to ambulate and require assistance after 10 to 15 years of MS evolution. Statins have been successfully used to treat cardiovascular diseases due to abnormal lipid profile. It is believed that statins exert their beneficial effects, at least partly, through an anti-inflammatory process. Multiple sclerosis is generally viewed as an inflammatory disease of the CNS caused by autoreactive antibodies against myelin. In a murine model of experimental autoimmune encephalitis (EAE), an experimental model for MS, atorvastatin has shown immunomodulatory activity that may be beneficial in MS treatment.Furthermore, simvastatin, another agent in the statin family, has shown promising effect in an open label study of the relapsing remitting form of MS (RRMS) in humans. A more recent study showed that Simvastatin treatment in patients with relapsing remitting MS was associated with a decrease the mean number of gadolinium enhancing lesions on MRI at months 4,5 and 6 of treatment compared to pre treatment MRI scans.All approved therapies for MS have profound immunological effects and employ immunomodulatory strategies. Due to a high toxicity profile and parenteral use, these agents are reserved for established disease. Avonex (interferon -1a) has been recently approved for patients presenting with CIS and magnetic resonance imaging (MRI) findings suggestive of MS. Interferon -1a requires weekly intramuscular injections and has a high toxicity profile. Due to the irreversiblity of the demyelinating process in CNS and high morbidity of MS, it is of great interest to develop early interventional measures that possess both ease of administration and a minimal toxicity profile. This study will also examine whether early intervention in patients with CIS may result in a state of immunological tolerance and whether atorvastatin has any residual effect after discontinuation. This may enable the patient to be withdrawn from therapy after a certain period of receiving treatment.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000052-46
Application #
7604615
Study Section
Special Emphasis Panel (ZRR1-CR-1 (01))
Project Start
2006-12-01
Project End
2007-09-16
Budget Start
2006-12-01
Budget End
2007-09-16
Support Year
46
Fiscal Year
2007
Total Cost
$262
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Al-Sofiani, Mohammed E; Yanek, Lisa R; Faraday, Nauder et al. (2018) Diabetes and Platelet Response to Low-Dose Aspirin. J Clin Endocrinol Metab 103:4599-4608
Grover, Surbhi; Desir, Fidel; Jing, Yuezhou et al. (2018) Reduced Cancer Survival Among Adults With HIV and AIDS-Defining Illnesses Despite No Difference in Cancer Stage at Diagnosis. J Acquir Immune Defic Syndr 79:421-429
Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H et al. (2018) Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int 93:1442-1451
Yanik, Elizabeth L; Hernández-Ramírez, Raúl U; Qin, Li et al. (2018) Brief Report: Cutaneous Melanoma Risk Among People With HIV in the United States and Canada. J Acquir Immune Defic Syndr 78:499-504
Aboud, Katherine S; Barquero, Laura A; Cutting, Laurie E (2018) Prefrontal mediation of the reading network predicts intervention response in dyslexia. Cortex 101:96-106
Kattan, Meyer; Bacharier, Leonard B; O'Connor, George T et al. (2018) Spirometry and Impulse Oscillometry in Preschool Children: Acceptability and Relationship to Maternal Smoking in Pregnancy. J Allergy Clin Immunol Pract 6:1596-1603.e6
Altekruse, Sean F; Shiels, Meredith S; Modur, Sharada P et al. (2018) Cancer burden attributable to cigarette smoking among HIV-infected people in North America. AIDS 32:513-521
Salemi, Parissa; Skalamera Olson, Julie M; Dickson, Lauren E et al. (2018) Ossifications in Albright Hereditary Osteodystrophy: Role of Genotype, Inheritance, Sex, Age, Hormonal Status, and BMI. J Clin Endocrinol Metab 103:158-168
Robert Braši?, James; Mari, Zoltan; Lerner, Alicja et al. (2018) Remission of Gilles de la Tourette Syndrome after Heat-Induced Dehydration. Int J Phys Med Rehabil 6:
Altman, Matthew C; Whalen, Elizabeth; Togias, Alkis et al. (2018) Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma. J Allergy Clin Immunol 142:1856-1866

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