Novel Drugs in a Pipeline for Progressive Multiple Sclerosis
Abstract
:1. Introduction
2. Time as a Key Element in the Treatment of PMS
3. New Potential Drugs in the Treatment of PMS
3.1. Biotin
3.2. Ibudilast
3.3. Simvastatin
3.4. Alpha-Lipoic Acid
3.5. Clemastine
3.6. Amiloride, Fluoxetine, and Riluzole
3.7. Masitinib
3.8. Opicinumab
3.9. Lamotrigine
4. Future Perspectives
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Trial | Intervention | Primary Outcome Measures | Secondary Outcome Measures |
---|---|---|---|
A Randomized, Double-blinded, Placebo-controlled Single-site Study of High Dose Simvastatin Treatment for Secondary Progressive Multiple Sclerosis: Impact on Vascular Perfusion and Oxidative Damage | Simvastatin 40 mg for first 4 weeks 80 mg (if tolerated) thereafter up to 17 weeks | Effect on cerebral blood flow | MRI: glutamate levels Adaptive Optics Scanning Laser Ophthalmoscope measurements of blood flow MRI: arterial spin labeling measurements of blood flow MRI: brain atrophy Clinical Outcome: EDSS |
A Phase III Randomized, Double-Blinded Clinical Trial Investigating the Effectiveness of Repurposed Simvastatin, Compared to Placebo, in Secondary Progressive Multiple Sclerosis, in Slowing the Progression of Disability | Simvastatin One (1 = 40 mg) tablet/day at night, for 1 month Two (2 = 80 mg) tablets/day at night, for the next 35 months Placebo Equivalent placebo | Time to the confirmed disability progression between simvastatin and the placebo arm based on changes in the EDSS scores compared to baseline | Response rate on the patient reported outcome form Multiple Sclerosis Walking Scale-12 version 2, Impact Scale-29 version 2 Cost effectiveness of intervention Change in the time taken to complete timed 25-foot walk Change in the time taken to complete the9 hole peg test Evaluating changes in the degree of disability based on the modified Rankin Scale Change in frontal lobe function based on frontal assessment battery scores Difference in the number and severity of multiple sclerosis-related relapse events between the treatment groups |
Lipoic Acid for the Treatment of Progressive Multiple Sclerosis | Lipoic acid 200 mg/day for 2 years Placebo taken daily for 2 years | Mobility: timed 25-foot walk | Mobility: timed 2-min walk Mobility: fall count Brain atrophy by MRI |
Assessment of Clemastine Fumarate as a Remyelinating Agent in Acute Optic Neuritis (ReCOVER) | Clemastine 12 mg (4 mg 3×/day) for 7 days followed by 8 mg (4 mg 2×/day) until 3 months Placebo Equivalent placebo | Change in P100 latency on full-field visual evoked potential Change in low contrast visual acuity | Change in retinal nerve fiber layer thickness on optical coherence tomography Radiological outcomes assessed by magnetic resonance imaging EDSS score |
Study | Treatment Method | Number of Patients and Duration | Results |
---|---|---|---|
Sedel (2015) [19] | Biotin 300 mg/day | 23 PMS patients 2–36 months | Positive |
Tourbah (2016) [20] | Biotin 300 mg/day compared to placebo | 154 PMS patients 12 months | Positive on EDSS/T25FW Negative on MRI |
Birnbaum (2017) [21] | Biotin 300 mg/day | 33 PMS and 10 RRMS patients 12 months | Negative, but older patients |
Cree (2020) [22] | Biotin 300 mg/day compared to placebo | 642 PMS patients 15 months | Negative |
Fox (2016, 2018) [30,31] | Ibudilast 100 mg/day compared to placebo | 255 PPMS and SPMS patients 96 weeks | Positive, but higher incidence of gastrointestinal disorders |
Chataway (2014) [34] | Simvastatin 80 mg/day compared to placebo | 140 SPMS patients | Positive on brain atrophy and EDSS No effect on the relapse rate, immunological markers, and MRI |
Spain (2017) [40] | Alpha-lipoic acid 1200 mg/day compared to placebo | 51 SPMS patients 2 years | Positive on brain atrophy No effect on the clinical outcomes, brain substructures and optical coherence tomography metrics |
Green (2017) [43] | Clemastine fumarate 5.3 mg/day compared to placebo | 50 MS patients 150 days | Positive on the P100 time delay in VEPs |
Vermersch (2012) [50] | Masitinib 3–6 mg/day compared to placebo | 35 PMS patients 12 months | Negative |
Kapoor (2010) [55] | Lamotrigine 400 mg/day compared to placebo | 120 SPMS patients 2 years | Positive on T25FW Negative on the mean change in cerebral volume |
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Sapko, K.; Jamroz-Wiśniewska, A.; Rejdak, K. Novel Drugs in a Pipeline for Progressive Multiple Sclerosis. J. Clin. Med. 2022, 11, 3342. https://doi.org/10.3390/jcm11123342
Sapko K, Jamroz-Wiśniewska A, Rejdak K. Novel Drugs in a Pipeline for Progressive Multiple Sclerosis. Journal of Clinical Medicine. 2022; 11(12):3342. https://doi.org/10.3390/jcm11123342
Chicago/Turabian StyleSapko, Klaudia, Anna Jamroz-Wiśniewska, and Konrad Rejdak. 2022. "Novel Drugs in a Pipeline for Progressive Multiple Sclerosis" Journal of Clinical Medicine 11, no. 12: 3342. https://doi.org/10.3390/jcm11123342
APA StyleSapko, K., Jamroz-Wiśniewska, A., & Rejdak, K. (2022). Novel Drugs in a Pipeline for Progressive Multiple Sclerosis. Journal of Clinical Medicine, 11(12), 3342. https://doi.org/10.3390/jcm11123342