Download Pragmatics of Actos in ASD

The Use of Actos® (pioglitazone) in
the Treatment of Autism Spectrum
Disorders
Whole Health & Wellness
Phillip C. DeMio, MD, Medical Director
Angela Shoemaker, Physician-To-Parent Liaison
733 Lakeview Plaza Blvd.
Suite G
Worthington, OH 43085
614-436-2036
320 Orchardview Ave.
Suite 2
Seven Hills, OH 44131
216-901-0441
© Phillip C. DeMio 04/08
Actos in ASD
 Actos is a Glitazone
 A group of medications marketed/approved for
diabetes in U.S. & internationally
 Off-label use for Immune System
 Variety of glitazones researched as such for
many years
 Employed clinically as such for 7 years
 Initally in MS, then others
 4 years now for ASD
What are the Actions of
Glitazones?
 Depends on the organ we’re considering
 Eg, pancreas vs. muscle vs. white blood cells
 Connects to which disease/symptoms we’re
considering
 Glitazones have their effects (including “side”
effects) no matter what we’re considering!
 This is true of all drugs and all supplements
and all treatments!
 Connects to off-label & novel uses of
medications and supplements
Consider White Blood
Cells as an Organ
 T-Lymphocytes
 Are white blood cells (WBC’s)
 The Generals of the Immune System
 Eg. Th-1 and Th-2
Excess Th-2 activity means
autoimmunity, allergy, and
lowered healthy immunity
What Happens in Kids with ASD
who have Abnormal Th-1/Th-2
Function?
 Immune dysfunction, autoimmunity and, allergy
in ASD affects:
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Brain/nerves
Gi tract/dysbiosis
Lungs/respiratory/sinus systems
Thyroid (and other hormonal organs)
Frequent severe infections/fever
Other/adult immune problems as mentioned
Allergy (skin, respiratory, food)
© Phillip C. DeMio, MD 2005
Abnormal Th-1/Th-2 Function,
cont’d
 This connects to variants of ASD:
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OCD
Tics/Tourette Syndrome
Immunity/autoimmunity/allergy (asthma)
RAD
Clinical and laboratory abnormalities
Parents, siblings, and other relatives of
persons with ASD (“later onset”)
Actos’s Effects on
Lymphocytes
 Actos shifts Th-2 back to Th-1
activity
 Apoptosis
 Now the generals can run the
troops properly!
 Ie, aim at the bad guys, no friendly
fire, and no civil war.
Goals in the Use of Actos
in ASD
 Improve the GI tract RE: leaky, & dysbiosis
 Reduce/eliminate frequent infections (But
Angie & Dr. D.: my kid never gets sick!)
 Reverse autoimmunity (brain, gi, thyroid, etc.)
 Improve or eliminate allergy (and steroids, and
aerosols, and antihistamine drugs…)
 Reduce viral load & dormant infectious agents
 The ultimate goal is better health and
cognition
Pragmatics of Actos in
ASD
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Tablets, patented, lactose, not SCD legal
Transdermal (Lee-Silsby)
Cost; Avandia
Diabetic kids with ASD: switch!
Actos has 15 & 30 mg sizes
Ramp the dose: begin with7.5 mg/day or less,
and go up, usually to 30 mg in 7.5mg jumps.
 I do not presume “target” doses: one size fits
none!
Pragmatics of Actos in
ASD
 Some patients sustain steady improvement
with no problems…
 But there are potential undesired (“side”)
effects with any treatment that is powerful
enough to help our kids!
 Early mild effects, almost expected include:
brief fever, GI “die-off (B & B),” and seeming
mild “viral” infections (with or without rashes)
Pragmatics of Actos in
ASD
 More intense undesired effects: prolonged high
fever, more marked signs of infection (viral
upheaval), regressions, brisk increases in
OCD’ish behavior, and diarrhea or abdomenal
pain
 Hypoglycemic-like effects and low metabolic
substrates: skinny kid, poor eater, intercurrent
illness (see above), PM dosing, &
mitochondrial/acidotic kids
 Fluid retention
 One child’s opisthotinos: ?pain, lactose, or
spasm
Pragmatics of Actos in
ASD: a Few Comments
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Overall safety
Comparing td with oral routes
Follow-up blood tests (organ support)
Time course of expected gainshow long
do we “wait?” (cases without intense
undesired effects)
 Blending with other therapies: HBOT,
LDN, antivirals, etc.
Pragmatics of Actos in
ASD
 Let’s revisit the cases that have intense
or brisk undesired effects
 “Foot in the door”
 What does it mean?
 Not throwing the baby out with the
bathwater
 PULSING the Actos!
Low Dose Naltrexone in
the Treatment of
Autism Spectrum
Disorders
Phillip C. DeMio, MD
320 Orchardview Ave.
Suite 2
Seven Hills, OH 44131
216-901-0441
www.drdemio.com
© Phillip C. DeMio, MD 2005
Low Dose Naltrexone
(LDN)
 Orginally for heroin addiction/opiate
addiction. (Depade®, formerly Trexan®,
ReVia®
 Concept behind such treatment
 Opiate receptors
 Drugs
 Endorphins/opiate peptides
© Phillip C. DeMio, MD 2005
Low Dose Naltrexone (LDN)
cont.
 “side” effects of such treatment
 Depressed mood
 Respiratory symptoms
 “hidden” immune toxicity
 Other abnormal immune symptoms: brain; others
 “sub clinical” rise in endorphins
 …but fully blocked by the high dose of Naltrexone
 This led to the syndrome of opiate/endorphin
withdrawal
-agitation
-respiratory (SOB, huffing, stuffy, cough)
-diarrhea/cramps
-“crawling skin”/gooseflesh
© Phillip C. DeMio, MD 2005
Opiate Peptides, Naltrexone,
and the Immune Connection
 T-Lymphocytes
 Are white blood cells (WBC’s)
 Eg. Th-1 and Th-2
 Excess Th-2 activity means autoimmunity, allergy,
and lowered healthy immunity
 Peptides
 Those from gluten, casein, and others
(“exorphins”) cause peptide-specific Th-2
stimulation (increased activity)
 That makes people sick! (symptoms in: ASD,
MS, ALS, IBD, HIV, RA, SLE, asthma, allergy,
and cancer to name a few)
© Phillip C. DeMio, MD 2005
Immune Connection cont.
 Endorphins
 Compete with exorphins
 So endorphins redirect Th-2 WBC’s away
from allergy/autoimmunity
 Endorphins also stimulate healthy immunity
(by heightening Th-1 activity)
 Endorphins are abnormally and strikingly
low in children and adults who have ASD
(and MS, ALS, IBD, HIV, RA, SLE,
asthma, allergy, and cancer)
(c) Phillip C. DeMio, MD 2005
Low-Dose Connection
 Recall the rise in endorphins with full dose
Naltrexone
 “side effects can be good” (a clue, a foot in
the door)
 But full dose Naltrexone blocks the
endorphins
© Phillip C. DeMio, MD 2005
Low-Dose Connection,
cont.
 Why the low dose?
 Naltrexone at low dose retains it abliity to
cause an endorphin rise
 If the dose is low enough, the endorphinblocking effect of Naltrexone is gone in as
little as two hours
 So most of the day yields higher endorphins
 They are not blocked
 They are free to “do good” (immune; other)
© Phillip C. DeMio, MD 2005
Low-Dose Connection,
cont.
 Great benefit for ASD (and MS, ALS, IBD,
HIV, RA, SLE, asthma, allergy, and
cancer)
 The dose:
 Less than one tenth the orginal dose used for
addiction.
 Currently the target doses are:
 3mg/24 hours if less than 45kg
 4.5mg/24 hours if over 45kg
 We will revisit “the”dose
© Phillip C. DeMio, MD 2005
LDN in Clinical use for
ASD
 Immune dysfunction, autoimmunity and, allergy
in ASD affects:
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Brain/nerves
Gi tract/dysbiosis
Lungs/respiratory/sinus systems
Thyroid (and other hormonal organs)
Frequent severe infections/fever
Other/adult immune problems as mentioned
Allergy (skin, respiratory, food)
© Phillip C. DeMio, MD 2005
Clinical use, cont.
 This connects to variants of ASD:
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OCD
Tics/Tourette Syndrome
Immunity/autoimmunity/allergy (asthma)
Clinical and laboratory abnormalities
Parents, siblings, and other relatives of
persons with ASD (“later onset”)
© Phillip C. DeMio, MD 2005
Clinical Use, cont.
 Preparations
 Topical or oral
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Currently, same dose for each
Swallowing, taste, and timing issues
11pm dose
Maybe oral is better if:
 Constipated
 Crampy
 Diarrhea: start with topical
 What about gluten and casein?
 Make exorphins
 LDN may cause withdrawal if not gf/cf
 But may actually cause improvement
 We will revisit the dose
© Phillip C. DeMio, MD 2005
Clinical Use, cont.
 Sources
 Coastal Compounding Pharmacy (topical)
 Lee-Silsby Compounding Pharmacy (topical
or oral)
 Others (experience/communication)
 Dr. McCandless after Dr. Bihari: Many
responders
 More science and numbers than Dr.
Kanner!
© Phillip C. DeMio, MD
What to Expect in Clinical
Use
 “Effects”
 Bowels and brain
 Immune system
 They overlap!
 “Side” effects
 Bowels and brain
 Immune system
 Stimulation
 “good”: endorphins/transient
 “not good”
 Die-off
 Excess blockade of endorphins
 Constipation/agitation/sensory issues
© Phillip C. DeMio, MD 2005
Other Clinical Issues
 Itching and rash
 Unique situations
 Opiate drugs
 Pain
 Anesthesia
 Clonidine/guanabenz
 Enzymes
 Long term
 Will effects sustain?
 Experience outside of ASD
© Phillip C. DeMio, MD 2005
Revisiting the Dose
 Kids/adults can get the “not good”
responses
 Some patients may not sustain
 Revisiting the dose
 Unsustained group
 Raise the dose (chasing your tail?)
 Pulse dose
 Kids on gf/cf diet
 Ultra-low-dose Naltrexone
 Start low and slow
© Phillip C. DeMio, MD 2005
LDN Conclusion
 Ultimately, as with other treatments
 Naltrexone helps many persons
 May help a little or a lot
 “effects” vs “side” effects
© Phillip C. DeMio, MD 2005
Transdermal DMSA
in the treatment of the
Autism Spectrum
Disorders (ASD)
© 5/06 Phillip C. DeMio, MD
320 Orchardview Ave, Suite 2
Seven Hills, Ohio
1st Monday of the Month at Noon Radio Show on Autism One
Radio, [email protected]
www.drdemio.com
What is DMSA? (2,3-mesodimercaptosuccinic acid)
 DMSA is a chelator
 What is a chelator?
 Chelators are substances that bind
metals and extract them from the body
(mostly into urine, stool and sweat).
 The process is called chelation and can
take anywhere from a few months to 2
years.
Why chelate in ASD?
Toxicity in ASD
 Mercury
 Vaccines
 Dental
 Diet/other
 Mercury is very toxic
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Brain
Immune system
GI tract
Metabolism
Reproduction, skin, eye,…
 “No matter what the cause…” (even when Hg
and others are detected, controversy remains)
Toxicity in ASD cont.
 Others Toxic Metals
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Lead
Aluminum
Thallium
Tungsten
Arsenic
Antimony, Tin, Bismuth
 They cause synergistic toxicity, in any known
combination
 If it weren’t for mercury, aluminum, vaccines,
and dental work these would not be nearly the
problem they are today.
Toxicity is ASD cont.
 Chelation and minerals treat Hg toxicity
 Simultaneous diagnostic information and
treatment (essential and multiple toxic minerals)
 Useful in treatment of ASD
 Clean up the diet and the home
 Other toxins
 Testing is difficult
 Treatment overlaps with that for heavy metals,
especially glutathione
 Clean up diet and home
Chelation
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Based on history, exam, and testing
Part of a whole program
Must supplement
“Side effects”: metabolic, renal, skin,
gi/fungal, cognitive
 Musical chairs with sulfur
 Topical vs. oral vs. IV; non-sulfur types
 Requires follow-up with lab testing
A brief history of chelation
and DMSA in treatment of
poisoning with Hg and other
metals
 Why sulfur? (Mercaptans)
 First Larger scale use of DMSA was to
replace IV EDTA in lead toxicity with an
oral treatment
 DMSA was almost simultaneously found to
be useful in toxicity with mercury and
cadmium
 Most of these cases were acute and
subacute
History of Chelation and
DMSA cont.
 Recall the toxicity issues with heavy
metals and ASD.
 This is repeated acute exposure, but the
result is a chronic problem
 This requires ongoing treatment (slow
and steady)
 S. Cave and others: oral protocols
Oral DMSA protocols
 Taste/swallowing issues
 GI issues
 “gi upset, irritation”, and other similar symptoms
 Yeast!
 Liver: why an oral issue? (less so with transdermal
DMSA)
 Labs
 Follow metals
 Hg and other toxic metals
 Nutritional metals (are the result of ongoing treatment)
 Liver, kidneys (not unheard of)
Why Transdermal DMSA?
 It works!
 Avoids oral aversions and many of the gi
issues (it and eg. IV GSH can sometimes
still stir up yeast)
 Other compliance/convenience points
(“asleep”, & etc,)
 “timed-released” naturally
Transdermal DMSA cont.
 Things to know:
 Use gloves (eg. pregnant mom)
 Odor
 Rashes
 Yeast
 Metals moving
 Can happen with any chelation (even
oral/nasal/drops/IV/”natural”)
Transdermal DMSA cont.
 Compounding R.Ph.
 Invented by Lee-Silsby
 85% vehicle
 Varies more than oral products from one shop
to another
 Dr. DeMio’s rule
 The pharmacist must talk to Dr. and parents
 Stability/quality/experience
Transdermal DMSA:
Other Considerations
 Generally use with GSH or NAC (routes)
 Brain Chelation: alpha-lipoic acid (topical), some others
 Use in other disorders: ADHD, OCD, ODD, Asperger’s
Syndrome, PDD(nos), RAD/adoptive issues, tics,
apraxias, LD’s, shadow syndromes
 Alzheimer’s Disease, MS, ALS, “neurodegenerative
disorders”
 Autoimmune: RA, SLE, IBD, severe “IBS,” severe
eczema; severe allergy, autoimmunity, hypoimmunity
 Cardiovascular Issues
Transdermal DMSA Followup: What do we look for?
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Labs (metals, metabolic)
Clinical (ie, not just on paper)
“side” effects (clinical, labs)
Chelation is a big commitment (doctor,
parent, patient)
 Time for Questions & Comments…