Save
A mouse model of progressive multiple sclerosis
Author(s): ,
R.L. Avila
Affiliations:
Renovo Neural, Inc., Cleveland, OH
,
D. Chmura
Affiliations:
Renovo Neural, Inc., Cleveland, OH
,
S. Lunn
Affiliations:
Renovo Neural, Inc., Cleveland, OH
,
S. Ramboz
Affiliations:
PsychoGenics Inc, Tarrytown, NY
,
H. Battapady
Affiliations:
Renovo Neural, Inc., Cleveland, OH; Department of Neuroscience, Cleveland Clinc, Cleveland, OH, United States
,
H. Dejesus
Affiliations:
Renovo Neural, Inc., Cleveland, OH
,
C. Erokwu
Affiliations:
Renovo Neural, Inc., Cleveland, OH
,
P. Harris
Affiliations:
Renovo Neural, Inc., Cleveland, OH
,
T. Elmer
Affiliations:
Renovo Neural, Inc., Cleveland, OH
,
S. Medicetty
Affiliations:
Renovo Neural, Inc., Cleveland, OH
B. Trapp
Affiliations:
Renovo Neural, Inc., Cleveland, OH; Department of Neuroscience, Cleveland Clinc, Cleveland, OH, United States
ECTRIMS Online Library. Avila R. Oct 9, 2015; 116369
Robin Avila
Robin Avila
Login now to access Regular content available to all registered users.

You may also access this content "anytime, anywhere" with the Free MULTILEARNING App for iOS and Android
Abstract
Discussion Forum (0)
Rate & Comment (0)
Abstract: P1519

Type: Poster LB

Abstract Category: Invited / Oral LB / Poster LB

Background: Multiple Sclerosis (MS) is the most common cause of non-traumatic neurological disability among young adults. Greater than 65% of relapsing/remitting MS patients (RRMS) eventually transition into a disease state where neurological decline is irreversible and continuous. Therapies are not available for these secondary progressive MS (SPMS) patients. A limiting factor in the development of therapies for SPMS patients is the lack of an animal model that shows progressive neurological decline.

Objective:
The objective of this study was to develop a rodent model of SPMS by investigating whether there is continuous neurological decline following repetitive cycles of demyelination.

Methods:
Eight-week-old C57BL/6J mice were subjected to one (SH), two (DH), or three (TH) cycles of 6-weeks of cuprizone- induced demyelination and 6-weeks recovery. The animals that received no cuprizone (CNT) and three cycles of cuprizone (TH) were tested for neurological disability at 62 and 77-weeks after the start of the first demyelination cycle. Animals were sacrificed for comprehensive histological analysis.

Results: The TH animals showed significant (P< 0.05) forelimb grip strength fatigue compared to CNT animals at 77-weeks but not at 62-weeks, demonstrating the progressive phenotype of the model. NeuroCube® system, a high-throughput platform to assess gait dynamics, revealed significant motor deficits in the TH mice compared to CNT animals at both 62 and 77-weeks. Furthermore, the differences in the motor function between the TH and CNT animals were larger at 77-weeks (P < 10-9) compared to 62-weeks (P < 10-7) demonstrating progressive decline in neurological function. Histologic and morphometric assessment of the brain tissue revealed a 70% decrease in the thickness (P< 0.001) of the corpus callosum (CC) and an 80% loss of myelinated axons (P< 0.001) in the CC in the TH animals compared to the CNT, demonstrating significant white matter atrophy.

Conclusion: Animals subjected to three cycles of demyelination (TH) demonstrate significant long-term motor deficits and fatigue. The total number of myelinated axons per volume of CC was 5-times lower in TH animals compared to age-matched controls. The behavioral deficits and white matter atrophy in this model resemble key features of progressive MS. Therefore, this model provides a platform to test therapeutics designed to slow continuous and irreversible neurological decline in progressive MS patients.

Disclosure:

Conflict of Interest: Robin Avila, Doug Chmura, Simon Lunn, Hiram DeJesus, Chino Erokwu, Paul Harris, Tasha Elmer and Satish Medicetty are full time employees of Renovo Neural, Inc. Harsha Battapady is an employee at the Cleveland Clinic.

Bruce Trapp is an employee of Cleveland Clinic and a consulting Chief Scientific Officer of Renovo Neural. Bruce Trapp received compensation as a speaker or consultant for EMD Serono, Novartis and Biogen.

Sylvie Ramboz is a full time employee of PsychoGenics Inc. PsychoGenics provides customized preclinical services focusing on psychiatric and neurodegenerative disorders, pain and inflammation, and spinal cord and traumatic brain injury. Renovo Neural provides contract research services on in vivo models of neuroprotection and remyelination. This project was supported by a grant from the International Progressive MS Alliance and Renovo Neural, Inc.

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings