The Use of Actos® (pioglitazone) in the Treatment of Autism Spectrum Disorders

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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   
Co nsi der White Blo od Ce lls a s a n Or gan
 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 K ids wit h ASD w ho have A bnormal T h1/ Th-2 Funct ion?
 Immune dysfunction, autoimmunity and, allergy in ASD affects:
       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
Abn ormal Th- 1/ Th- 2 Functi on, cont’ d
 This connects to variants of ASD:
      OCD Tics/Tourette Syndrome Immunity/autoimmunity/allergy (asthma) RAD Clinical and laboratory abnormalities Parents, siblings, and other relatives of persons with ASD (“later onset”)
Acto s’s Ef fects o n Lymp hocyt es
 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 th e Use o f 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
Pr agmatics of Ac tos i n ASD
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!      
Pr agmatics of Ac tos i n 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)
Pr agmatics of Ac tos i n 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
Pr agmatics of Ac tos i n ASD : a Few Co mme nts
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.    
Pr agmatics of Ac tos i n 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 Na lt re xone in the Tr eatm ent o f Au tism Sp ectru m Diso rders
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 Do se Naltr exone (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
 “side” effects of such treatment
 Depressed mood  Respiratory symptoms
Low Dose Nal trexone (LDN) cont .
 “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
Opi ate Pe pt ides , Nal trexone, and the Immune Connecti on
 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
Imm une Co nnectio n 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-Do se Connectio n
 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-Do se Connectio n, 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-Do se Connectio n, 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
LDN in Cli nic al u se fo r ASD
 Immune dysfunction, autoimmunity and, allergy in ASD affects:
       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
Cli nical u se , cont.
 This connects to variants of ASD:
     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
Cli nical Use , cont.
 Preparations
 Topical or oral
    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
Cli nical 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 Ex pect in Cli nical 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
Ot her Cli nic al I ssues
 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
Re visit ing t he Do se
 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 Co nclu sio n
 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
Tr ansd er mal DM SA in the tr eatment of the A utism Sp ectr um Diso r der s (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, pdemio@autismone.com www.drdemio.com
What is DMS A? (2, 3meso -di mer captosucci nic aci d)
 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 Brain Immune system GI tract Metabolism Reproduction, skin, eye,…
 Mercury is very toxic
 “No matter what the cause…” (even when Hg and others are detected, controversy remains)
To xicit y in ASD c ont.
 Others Toxic Metals
      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.
To xicity is ASD c ont.
 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
Ch elatio n
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 bri ef hi story of chel ati on a nd DMSA in treat ment of poi soni ng with Hg and other met als 
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
Hi story o f Chel ati on and DMS A co nt.
 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
Ora l 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 Tra nsd ermal DM SA?
 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
Tr ansderma l DMSA cont.
 Things to know:
     Use gloves (eg. pregnant mom) Odor Yeast Metals moving Can happen with any chelation (even oral/nasal/drops/IV/”natural”)
 Rashes
Tr ansderma l DMSA cont.
 Compounding R.Ph.  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
 Invented by Lee-Silsby
Transdermal DMSA: Other Co nsid erati ons
 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 Fol low -up: What do we look for?
    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…