High-Dose B Vitamin Supplementation as a Disease-Modifying Therapy in Alzheimer Disease

Abstract KARS encodes lysyl-tRNA synthetase, which is essential for protein translation. KARS mutations sometimes cause impairment of cytoplasmic and mitochondrial protein synthesis, and sometimes lead to progressive leukodystrophies with mitochondrial signature and psychomotor regression, and follow a rapid regressive course to premature death. There has been no disease-modifying therapy beyond supportive treatment. We present a 5-year-old male patient with an asymmetrical leukodystrophy who showed overt evidence of mitochondrial dysfunction, including elevation of lactate on brain MR spectroscopy and low oxygen consumption rate in fibroblasts. We diagnosed this patient's condition as KARS-related leukodystrophy with cerebral calcification, congenital deafness, and evidence of mitochondrial dysfunction. We employed a ketogenic diet as well as multiple vitamin supplementation with the intention to alleviate mitochondrial dysfunction. The patient showed alleviation of his psychomotor regression and even partial restoration of his abilities within 4 months. This is an early report of a potential disease-modifying therapy for KARS-related progressive leukodystrophy without appreciable adverse effects.

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Possible Consequences of the Approval of a Disease-Modifying Therapy for Alzheimer Disease

JAMA Neurology ◽

10.1001/jamaneurol.2020.4478 ◽

2020 ◽

Author(s):

Erik S. Musiek ◽

John C. Morris

Keyword(s):

Alzheimer Disease ◽

Disease Modifying Therapy ◽

Disease Modifying

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High-Dose B Vitamin Supplementation and Progression of Subclinical Atherosclerosis: A Randomized Controlled Trial

Journal of Vascular Surgery ◽

10.1016/j.jvs.2009.10.097 ◽

2009 ◽

Vol 50 (6) ◽

pp. 1527 ◽

Cited By ~ 1

Author(s):

H.N. Hodis ◽

W.J. Mack ◽

L. Dustin

Keyword(s):

Randomized Controlled Trial ◽

Controlled Trial ◽

Subclinical Atherosclerosis ◽

Vitamin Supplementation ◽

High Dose ◽

Randomized Controlled ◽

B Vitamin

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Residual disability after severe relapse in people with multiple sclerosis treated with disease-modifying therapy

Multiple Sclerosis Journal ◽

10.1177/1352458518809903 ◽

2018 ◽

Vol 25 (13) ◽

pp. 1746-1753 ◽

Cited By ~ 5

Author(s):

Anat Achiron ◽

Ida Sarova-Pinhas ◽

David Magalashvili ◽

Yael Stern ◽

Aviva Gal ◽

...

Keyword(s):

Multiple Sclerosis ◽

Neurological Status ◽

High Rate ◽

High Dose ◽

Disease Modifying Drugs ◽

Disease Modifying Therapy ◽

Disability Status ◽

Relapsing Remitting ◽

Disease Modifying ◽

Relapsing Remitting Multiple Sclerosis

Background: The rate of post-relapse residual disability in patients with relapsing–remitting multiple sclerosis (RRMS) treated with disease-modifying drugs (DMD) has not been studied. Objective: To assess relapse residual disability in DMD-treated RRMS patients. Methods: We followed DMD-treated RRMS patients presenting with acute relapse who received high-dose steroids. Increases in Expanded Disability Status Scale (EDSS) of at least 2.0, 1.0–1.5 or 0.5 were defined as severe, moderate or mild relapses, respectively. The proportions of patients with post-relapse residual disability defined as the failure to regain pre-relapse neurological status at 1, 4 and 12 months were evaluated. Results: Out of 1672 relapses in DMD-treated RRMS patients, 17% were severe. In patients who presented with a severe relapse, we observed post-relapse residual disability of at least 1.0 EDSS point in 60.1%, 55.9% and 48.2% of patients at 1, 2 and 12 months of follow-up, respectively. Post-relapse residual disability of at least 2.0 EDSS points was observed in 37.4%, 30.7% and 20.7% of patients after 1, 2 and 12 months, respectively. Conclusion: A high rate of incomplete recovery was seen 12 months following severe relapse among RRMS patients and may contribute to the accumulation of long-term disability.

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