BIOC 095 Multiple Sclerosis: Treatment Throughout A Lifetime Flashcards
13 Oct, 2017
Noon - 1pm
- University of Vermont School of Medicine - Hill Panitch Lectureship
- John R. Corboy, MD
Goal of MS therapy
- Life-long
- Brain / spine
- Health
Approach to MS
- avoid developing it, i.e. Find cause and stop it
- alter immune sys function
protect nerves frm degeneration - enhance normal repair in CNS
- replace damaged cells in CNS
- good behaviors
Natural progression of MS
- Life-long time
- Relapsing forms:
1. Subclinical
2. Mono-symptomatic- initial demeaning event
3. Relapsing remitting - clinically definite MS
4. Secondary progressive - relapse - increase lv of disability over time & accumulated MRI lesion burden
- increase cognitive dysfunction
- decrease in brain volume
Gray matter lesions in MS
- Leukocrotical
- Intracortical
- Subpial, superficial
Meninges B-cell follicles
- Meningeal inflammation > widespread
- link to cortical pathology in MS
Affect activity (survey in women patients)
- General activity level diminish after MS diagnosis
Radiologically isolated syndrome
- 1/3 will develop clinical MS over 2-5yrs
- 91% develop radio graphic dissemination over 6-30months
- Male > female
- Smaller total brain volume and cortical volume
Risk factors in early MS rise MS
- Genetic (>200) & env risk factors (EBV, smoking, obesity, Vit D)
- 1st degree relatives w/ 10-20 fold increase risk
- Study:
- 300 asymptomatic FDRs of MS patients, 18-30
- Env screen, blood (E8V, Vit D, HLA, SNP, immunological & neuronal damage markers); activity monitor
- Brief screening MRI, brain & C spine
- Compare those w/ vs those w/o MRI c/w MS
- Similar to GEMS (Genes & environment in MS)
Treatment
- 1st attack: damage > similar to radiologically
- Associate w/ NfL lvl
Treatment effect on brain atrophy correlates w/ treatment effect on disability in MS
- High correlation
Net change in expanded disability status scale (EDSS) score frm before an exacerbation to aft
- 42.4% increase 0.5+
- 28.1% increase 1+
> Relapse has significant relationship w/ disabilities
> Relapse in early age influences increase
Vocab
DSS 3, DSS 6, DSS 8
DMT benefits
Decrease:
- relapses
- new /active MRI lesions
- brain volume loss *esp important
- disability progress due to attacks
- no. Failing NEDA
- can't ognitive deterioration
- all approved and effective in RRMS
- approved in CIS
- Only ocrelizumab approved for progressive MS
(Some benefits documented w/ other DMTs)
* DMTs are less efficacious as people ageMean age in MS treatment
- Ocrelizumab OPERA I/II Hauser 2017: mean age = 36
- Another Ocrelizumab: mean age = 47
Vocab
- dimethyl fumarate
- natalizumab v Pb
EU vs NA treatment difference
- NA almost no diff. btw placebo gp & treatment gp
- EU > diff (becoz EU = younger, early onset, relapses more
> gain benefits - W/ relapses> benefit
- <51 age + Gad lesions > gain more benefits
Is it safe to discontinue DMTs in MS?
- Outcomes: % with new relapse or T2/FLAIR lesion,
% w/ EDSS change, patient reported outcomes
> Safe to DC
Progressive MS
- May b thought of as aging transplanted onto MS
- Possibly due to loss of cellular energy production & oxidative stress of cells
- Early studies w/ Biotin (Vitamin B-7), alpha-lipoid acid, & Zocor
Chronic
- Increase energy demand & sodium accumulation in the atonal cytoplasm
- Increase exposure to toxic species
Ref: 2016 PMID:27889191
Targeting demyelination & virtual hypoxia w/ high-dose biotin as treatment
Myelin / atonal damage
- Oxidation
- anti-oxidants e.g. A lipoid acid, sim a station
- Microglial active > destructive pro-inflammmatory cytokines
- Dysfunction of voltage-gate channels
- Use Biotin as a co-enzyme in Krebs cycle
Neuroprotective effects of lipoid acid in SPMS
Results of a placebo-controlled pilot trial
- LA = an inexpensive, oral antioxidant > water & fat-soluble
- 2 year RCT of lipoid acid 1200 mg daily vs placebo
- % change brain volume 66% reduction
Conclusions
- Protect the cells frm die > good way to treat MS patients
- Younger patient benefits
- Good behaviors (no smoking, regular exercises)
- Imunotherapy ??? In late progression (Age)
