神經退化性疾病的新醫療觀
Functional therapeutics in
Neurodegenerative disease
神經內科
張嘉祐 醫師
WHAT IS FUNCTIONAL MEDICINE
?
Functional medicine is a science-based ,
healthcare approach that assess and
treats underlying causes of illness
through individually tailed therapies to
restore health and improve function.
Science-Base Field of Health Care:
The Principles
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Biochemical Individuality Based on Genetic
and Environmental Uniqueness
Patient-Centered versus Disease-Centered
Dynamic Balance of Internal and External
Factors
Web-like Connections of Physiological Factors
Health as a Positive Vitality
Not merely the Absence of Disease
Promotion of Organ reserve-healthspan
Complexity theory:
The study of chaos
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Nonlinear dynamics : a weblike model
Small changes in initial conditions lead to
large changes in outcome(butterfly effect)
Pattern recognition in chaotic systems
analysis and prediction of trends
Human beings are complex systems;
disease are complex “emergent” patterns.
PATIENT WORKUP
Nutritional Status
Immune/Inflammation
Oxidative stress
GI Function
Detoxification
Structural
Neuro-Endocrine
Mind－Body
SIGNS
SYMPTOMS
MEDIATORS
TRIGGERS
ANTECEDENTS
Patient Centered Assessment
Mediators, Triggers and Antecedents
Antecedents
(genetics,experiences,past
Illnesses,occupation,
Demographic,nutrition, life style)
Triggers
(microbes,allergens, trauma,
Toxins)
Biological Mediators
(cytokines,prostanoids,ions,
NO,kinins,hormones,
Neurotransmitters, Free radicals)
Alzeimer’s Disease Prevalence
9
8
7
6
affected
individuals
(millions)
5
4
3
2
1
0
1930 1950 1970 1990 2010 2030
Parkinson’s disease-New
perspectives
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Individuals with specific genetic defects
causing hepatic detoxification enzyme
dysfunction may develop Parkinson’s
disease as a result of exposure to
certain environmental xenobiotic
chemicals proving neurotoxic
Parmacogenetics:a laboratory
tool for optimizing therapeutic
efficiency
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Parmacogenetics is the study of the
linkage between an individual’s
genotype and that individual’s ability
to metobolize a foreign compound.
Clinical Chemistry 43:2 254-266 (1997)
Genetically determined differences in
Xenobiotic metabolism as a risk factor in
Parkinson’s disease
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Patients with inherited CYP2D6
cytochrome P450 enzyme
deficiency had 2.4 X increased risk
for Parkinson’s disease
Fundam appl Toxicol, 1996 (30)
Xenobiotic metabolism in
Parkinson’s disease
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Severe deficiency of sulfate
conjugation in 70% of PD subjects
PD may be unusually susceptible to
exogenous or even endogenous toxins
Neurology, July, 1989
Exotoxins in Parkinson’s
disease
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MPTP
Manganese
Copper
Carbon Monoxide
Organic solvents
Pesticides
Aging, Energy, and Oxidative Stress
in Neurodegenerative Disease
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Energy metabolism
Excitotoxicity
Oxidative damage
Combination of therapies that act at
sequential steps may have proved
efficacy
M.Flint Beal Ann Neurology 1995;38:357-366
Functional Therapeutics In
Neurodegenerative disease
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Mitochondrial Resuscitation
Liver Detoxification
Free radical scanvengers
Neurotrophic factors
Using both genetic and biochemical
markers to identify patients at risk for
neurodegenerative disease.
Mitochondrial Resuscitation –
improved mitochondrial function
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Coenzyme Q10
NADH
Phosphatidylserine
daily dose
120 mg
5 mg twice
100 mg
Low 【coenzymeQ10】
Reduced Complex I Activity
Increased ROS Formation
Coenzyme Q10 (ng/mg protien) in platelet
mitochondria
Shults, C.W. Ann Neurol, August, 1997, 42:261-64
250
200
150
100
50
0
PD
SPOUSE
CONTROL
Clinical and biochemical correlations in
mitochondrial myopathies treated with
coenzyme Q10
Bresolin,N. Neurology, June, 1998
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Kearn-Sayre syndrome and chronic
progressive external opthalmoplegia
One year CoQ10 120mg per day
Reduction of lactate and pyruvate levels
following exercise
Generally improved neurologic function
Nicotinamide Adenine
Dinucleotide(NADH)A New Therapeutic Approach to
Parkinson’s Disease
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Of 885 patients who received NADH,
80% show “moderate to excellent”
improvement in their disability
Effects of phosphatidylserine in ageassociated memory impairment
Neurology 41:644-49, 1991
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Phosphatidylserine is one of the key
components of neuronal membranes.
A marked improvement on performance
tests related to memory and learning in
a group of 149 memory impaired
patients treated with phosphatidylserine
for 12 weeks.
Liver Detoxification
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Parkinson’s patients manifest flaws in
their ability to detoxify various
chemicals to which they are exposed.
Glutathione is one of the most
important components of the liver’s
detoxification system.
N-acety-cysteine (NAC), Vitamin E and
C, alpha lipoic acid, and herb silymarin
Reduced glutathione in the treatment of
early Parkinson’s disease
Prog Neuropsychopharmacol Biol Psychiatry 20(7): 1159-70, 1996
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Intravenous glutathion twice daily for
30 days.
All patients improved significantly after
glutathione therapy with 42 % decline
in disability
Once glutathione stopped, the
therapeutic effect lasted 2-4 months.
Free radical scanvengers –
Antioxidants
Vitamin E
Vitamin C
Alpha lipoic acid
Vitamin D
N-acety-cycteine
Acety-L-carnitine
Ginkgo bioba
1200 IU
800 mg
80 mg
400 IU
400 mg
400 mg
60 mg
A pilot trial of high-dose antioxidants
in an attempt to slow the progression
of Parkinson’s disease
Ann N Y Acad Sci 570:186-96,1989
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Evaluate the effectiveness of vitamin E
and C in a large group of Parkinson’s
patients over several years.
The time until patients to required Ldopa therapy was extended 2.2 years.
A placebo-controlled, double-blind
randomized trial of an extract of
Ginkgo biloba for dementia
Le Bars, P JAMA October 22, 1997
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137 patients, 52 weeks, Egb 120mg/d
27 % treated group improved on
standardized cognitive testing
Egb actions: homeostasis of
inflammation, membrane protection,
neurotransmission modulation
for
antioxidant enzymes in rat brain
cortex
Kotler, M.
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Pineal Research , March, 1998
Increased levels of mRNA for
glutathione peroxidase, copper-zinc
superoxide dismutase, manganese,
superoxide dismutase
More marked increase with chronic
treatment.
Once effective treatments are established,
future prospects will include using both genetic
and biochemical markers to identify patients at
risk for neurodegenerative illnesses, so that one
can initiate therapy at a presymptomatic stage
and hopefully prevent the illness.
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