Model: G93A High Copy
Study start date: 12/2/2002
Study completed date: 3/14/2003
Formulation point person: Mukur Gupta
In Vivo point person: Erin Williams
Rationale: Desipramine is FDA approved as a tricyclic anti-depressant. It’s used in the treatment of eating disorders like bulimia and in treating symptoms of diabetic neuropathy. It increases the level of IL-10 in a dose dependent manner. Inflammation is known to be a major culprit in ALS and IL-10, in Phase II clinical development , is a potent inhibitor of inflammation. Treatment with IL-10 prevented CNS inflammation in several models of neurodegeneration such as EAE, SCI, TBI and global ischemia via marked reduction of TNF-alpha, functional recovery and neuroprotection. As an anti-inflammatory cytokine, IL-10 may prevent glial activation and neuronal death and may be a possible treatment for ALS. IL-10 is known as the master anti-inflammatory cytokine or cell signaling protein. It’s an off switch for inflammation.
Notes: Desipramine is an IP study - 1x/d; 7d/wk - Day 50 start ....
Conclusions: Endpoints scored include mortality, neurological score and body weight. Results: Desipramine treatment resulted in a possible but weak positive trend in survival in litter matched treated males. Treated females show a positive trend in neurological score. No differences were observed in all other endpoints for either sex group. Desipramine has excellent CNS penetration. "
"Methods: A placebo controlled, double blind, randomised study carried out in five United Kingdom centres on outpatients with clinically definite multiple sclerosis, measurable disability on Guy's neurological disability scale (GNDS), no relapse in the preceding six months, and not on antidepressant drugs. Over 24 weeks all patients received vitamin B-12, 1 mg intramuscularly weekly, and either lofepramine 70 mg and L-phenylalanine 500 mg twice daily, or matching placebo tablets. Outcome was assessed using the GNDS, the Kurtzke expanded disability status scale; the Beck depression inventory, the Chalder fatigue scale, and the Gulick MS specific symptom scale.
Conclusions: Patients with multiple sclerosis improved by 2 GNDS points after starting vitamin B-12 injections. The addition of lofepramine and L-phenylalanine added a further 0.6 points benefit. More research is needed to confirm and explore the significance of this clinically small difference. "
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