umdf winter 2005 final · worms with mitochondrial diseases bernard lemire, ph.d. department of...

United Mitochondrial Disease Foundation

Volume 10 � Issue 1 � Winter 2005

My research lab studies mitochon-drial diseases and dysfunction inworms. Rather obscure and not terriblyuseful, you think? How can researchon worms help us better understand andtreat mitochondrial diseases in humans?Energy generation by mitochondria issuch a fundamental process to life thatit is highly similar in all animals. Themitochondrial respiratory chain (MRC)consists of a series of complex proteins(called complexes I to V) that converthigh-energy electrons into ATP, theenergy currency of most cells (See Fig.1 on 0). Most of these high-energy electrons, derived from foods

Worms with MitochondrialDiseases

Bernard Lemire, Ph.D.Department of Biochemistry

University of AlbertaEdmonton, Alberta, Canada

UMDF Grant Recipient 2003

ITOCHONDRIAL EWSNM

Chapter NewsSee pages 4-6

DevelopmentCorner

See page 7

Adults Corner See page 16

?Ask theMito Doc

See Page 2

Alabama 5K Raisesmore than $34,000

McLeod and Peek FamiliesPictured Above

More Fundraisers on Pages 11-12

Continued on page 10

By Popular DemandEnergy Bands are

HERE!These silicone bracelets are UMDF-green and encircled with

! Energy for Life ! www.UMDF.orgThe bracelets are a great way to raise awareness and

support those affected by mitochondrial disease.

You can order online at www.umdf.org or contact the office at 412-793-8077 or email [email protected] for an order form.

Cost is $4 each (postage and handling included)OR

Package of 10 bracelets for $10 (plus $5 in postage and handling)Get your friends together and split the cost!

Mark your Calendars NOW!

Mitochondrial Medicine 2005

Gateway to a CureScientific Sessions:

June 15-17, 2005

Family Sessions: June 17-18, 2005

Clinician Sessions: June 18, 2005

Hyatt Regency Union Station St. Louis, Missouri

Scientific Program ChairBruce H. Cohen, MD

Call for Abbstractswww.umdf.org/conferences

See Pages 8 & 9

2 Mitochondrial News Winter 2005

Living with mitochondrial diseasepresents many twists and turns - amaze of questions. UMDF is pleasedto offer answers to some of thosequestions. All questions and responsesare taken from www.umdf.org -- Askthe Mito Doc. Please note thatinformation contained in Ask the MitoDoc is for informational andeducational purposes only. Suchinformation is not intended to replace,and should not be interpreted or reliedupon, as professional advice, whethermedical or otherwise.

Responders for this issue: Gerard T.Berry, MD, Jefferson Medical School,Philadelphia, PA and Amy Goldstein,MD, Children�s Hospital of Pittsburgh.

The Question is: Our daughter who is two and a half is

suspected of having a metabolic disorder.The geneticist is leaning toward themitochondrial area. Our daughter ishypotonic, has severe reflux, globaldevelopment delays, heat intolerance,abnormally high pain tolerance, majorregression after an illness and hasbalance problems. She cannot sit aloneor stand alone. She has shown lowcarnitine levels and had elevatedmethomylonic acid levels during anillness. It has been suggested that wehave a fundoplication. We would like tohave more information from doctors whodeal with these types of issues and howthey will affect this procedure. What arethe positive and negative issues? Ourdaughter can have bouts of vomitingsometimes up to forty times a day on abad day. We have had a scope done ofthe esophagus and there was no damage.She does have a hiatal hernia. Anyinformation you could share would bevery valuable to our family. Response From:Gerard T. Berry, MD

There are at least 2 issues. The firstone is the need to establish in yourdaughter the correct diagnosis. And the

second is the need to provide the optimaltreatment for gastroesophageal reflux(GER). The latter is most important as itis possible that a specific diagnosiscannot be made, but she needs the propersymptomatic treatment.

All of her clinical problems arecompatible with a primary defect inmitochondrial oxidative (Ox-Phos)metabolism. The intermittentelevation in methylmalonic (MMA) acidlevels may also be seen in mitochondrialOx-Phos disorders. However, the MMAphenomenon may increase the likelihoodthat a specific diagnosis will not bemade. As an aside, it is important that aprimary defect in vitamin B12metabolism be ruled out as well sincethey can be associated with intermittentelevation of urine MMA. Finding a highlevel of MMA and the amino acid,homocysteine, in plasma would indicatea defect in vitamin B12 as the cause ofher problems. The main reason forfinding the underlying metabolic cause,be it Ox-Phos or Vitamin B12, is that aspecific therapy might help the vomitingand GER get better or even disappear.

Metabolic problems of many differenttypes are associated with recurrentvomiting. And hypotonia from any causemay predispose an infant or child toGER and hiatal hernia. It is imperativethat you work closely with anexperienced pediatric gastroenterologistin making the decision whether afundoplication is performed. It would bethe logical procedure to do for GERalone or associated with minimal tomoderate regurgitation. But if thevomiting is truly relentless and violent, itmay, at the least cause the fundoplicationto break down and, at the worst, causetears or rupture of the stomach, if anatural outlet has been artificiallyobstructed and is necessary to expel thestomach contents during the course ofuncontrolled vomiting. You all must usegood judgment. The Question is:

I am aware that there are differentmedications that people with mitodisorders should avoid; however, I amnot familiar with all of them. In myconcern to avoid potential problems, isthere a "list" of medications to avoid? Response From:Amy Goldstein, MD

There are certain medications to takecautions with when you have amitochondrial disorder. This is not anexhaustive list and does not pertain toevery patient with a mitochondrialdisorder. Review your individualdisorder and medications with yourpersonal physician.

Prior to any surgical procedure,review your medical history with theanesthesiologist. Certain anesthetics usedin surgical procedures should be usedwith caution, and these should bereviewed with the anesthesiologist. Thedecision about whether to use specificdrugs must be based on your disorder,your age, and the surgical procedurebeing performed. A review is provided in"Think Mitochondria" by Drs. BruceCohen, John Shoffner, and GlennDeBoer, reprinted from the Spring 1998UMDF Newsletter, and is available bycalling the UMDF office. Patients withmitochondrial disorders could be at riskfor a condition called malignanthyperthermia, and there is a protocol forthe anesthesiologist to follow for thiscondition.

Valproic acid (Depakote) has beenused as an anti-seizure medication insome patients safely; however, it has ledto serious and fatal consequences inother patients. It should be avoided inthe very young patient, especially whenthe diagnosis is uncertain. However, if apatient has been on Depakote withoutproblems, with careful monitoring, it isgenerally safe to continue on thismedication. Depakote can deplete thecarnitine stores, so Carnitine should besupplemented while on Depakote.

If IV fluids are necessary, LactatedRingers solution should be avoided as itcontains lactic acid.

Antiretroviral drugs (anti-HIV drugs)are toxic to mitochondria and should beavoided if possible.

Doxorubicin, a chemotherapymedication, causes cardiomyopathy as aside effect, most likely throughmitochondrial damage, and should beavoided.

Aminoglycoside antibiotics, such asgentamicin, streptomiycin andtobramycin, can induce hearing loss bydamaging mitochondria. This accountsfor 5-10% of drug-induced deafness and0.6% - 2% of the deafness population.These antibiotics should be avoided ifthe cause of the mitochondrial disorderis unknown. There are specific pointmutations in the mtDNA that make onemore susceptible to this ototoxicdamage.

Certain antipsychotic medications canincrease the risk of diabetes and shouldbe used with caution and frequentmonitoring.

Medications can be essential to yourhealth and well-being. Please review anyconcerns you have with your physician.More information can be obtained fromthe UMDF website and throughliterature available from the UMDFoffice.

?Ask the

Mito Doc

3Mitochondrial News Winter 2005

Chairman�s Report Board of TrusteesCharles A. Mohan, Jr. - Chairman

John DiCecco - Vice ChairmanStan Davis - TreasurerNick Rillo, Secretary

Bruce H. Cohen, M.D.Gerald A. Cook, Esq.

Charles L. Hoppel, M.D.Richard W. Kubach, Jr.

Joe RiceMary Pisani

Sharon ShawW. Dan Wright

Scientific Advisory BoardMichael J. Bennett, Ph.D., FRCPath,

DABCCGerard T. Berry, M.D.

Richard G. Boles, M.D.Salvatore DiMauro, M.D.

Annette Feigenbaum, M.D.,MBChB,FRCPC

Carol Greene, M.D.Andrea Gropman, M.D.

Richard H. Haas, M.B., B.Chir.Richard Kelley, M.D., Ph.D.

Douglas S. Kerr, M.D., Ph.D.Arnold Munnich, M.D., Ph.D.

Robert K. Naviaux, M.D., Ph.D.David Nicholls, Ph.D.

William Nyhan, M.D., Ph.D.Brian Robinson, Ph.D.

Russell P. Saneto, D.O., Ph.D.Eric Schon, Ph.D.

John Shoffner, M.D.Eric A. Shoubridge, Ph.D.

Keshav Singh, Ph.D.Jan Smeitink, M.D., Ph.D.

David Thorburn, Ph.D.D.M. Turnbull, M.D., Ph.D.

Rajiv R. Varma, M.D.Georgirene Vladutiu, Ph.D.Douglas C. Wallace, Ph.D.Kendall B. Wallace, Ph.D.

David Whiteman, M.D.

WORMS, MICE, YEASTMoney, time and effort for the

study of worms, mice and yeast! Is itreally necessary to spend hard earnedmoney studying worms, mice andyeast? How long will we be fundingresearch on worms, mice and yeastbefore we see clinical applications?

It wasn't until I read the leadarticle in this issue of MitochondrialNews, written by UMDF grantrecipient Bernard Lemire, Ph.D., thatI realized the importance and reasonfor studying worms, mice and yeast.

Dr. Lemire writes, "Energygeneration by mitochondria is such afundamental process to life that it ishighly similar in all animals." Sosimilar in fact that this simplest of allanimals, the worm, actually generatesenergy (ATP) via the respiratorychain in much the same way as wedo.

Worms, mice and yeast are readilyaccessible, affordable, easy to grow,small enough to carry around on adish and, as of this writing, are notprotected by labor unions oradvocacy groups. They are the"guinea pig" of choice.

Researchers like Dr. Lemire,working with worms, mice and yeast,will have an impact that willsomeday provide clinical applicationsfor easier diagnosis, better treatmentsand ultimately a cure formitochondrial disease.

It's amazing that something assmall as mitochondria, sub-cellularorganelles 1/30,000th of an inchlong, can have such an impact on ourquality of life. Consider that it takesabout 3,000,000,000,000,000,000 (3Quintillion) molecules of ATP eachsecond just to keep a human aliveand that there are 10,000,000,000 (10Billion) cells in the body containingan average of 600 mitochondria percell. Therefore each cell must makeabout 5,000,000 (5 million)molecules of ATP each second andeach mitochondria in that cell must

UMDF MISSIONTo promote research and

education for the diagnosis,treatment and cure of

mitochondrial disorders and to provide support to

affected individuals and families.

produce, onaverage, 8,333molecules of ATPeach second just tokeep us alive. Nowonder these smallmechanisms arecalled the powerhouse of the cell, and no wonder whya "glitch" in this process can havesuch varied results adverselyaffecting the quality of life inpatients.

Hmm, if worms, mice and yeastare all that "simple" and yet thatsimilar to us, perhaps we're not ascomplex as we think! Worms, miceand yeast � lions, tigers, and bears!

Toward a cure,

Charles A. Mohan, Jr.

Newsletter EditorKara [email protected]

In Memory of ...This issue of MitochondrialNews is being dedicated toChana Scholl, 10-15-57 to

2-3-05. Chana was thefounder of the COX

Foundation which was thenucleus for the formation

of UMDF.

The UMDF BoardOn page 12, you will find a

brief description of the UMDFBoard of Trustees and their

roles in the foundation. If youwould like to pose a questionfor our trustees, please sendthem to [email protected] or

mail them to UMDF, Attn: Kara,8085 Saltsburg Road, Suite201, Pittsburgh, PA 15239.More information about the

Board is available atwww.umdf.org (About UMDF).

Upcoming Events� April 30, 2005 - Race for Riley,Whatever it Takes 5K Walk/Run andTot Trot, Georgia Baptist Children�sHome in Palmetto, GA. For moreinfo, call Waynette & Rodney Peekat 770-463-0714 or [email protected].

� May 2005 - Benefit Dinner


Chapter ActivitiesNEW YORK METROCHAPTERManhattan, NYPresident: Mary PisaniPhone: 203-287-0655Email:[email protected]

NEW ENGLAND CHAPTERBoston, MAPresident: Bridget WillisPhone: 413-593-5920 (Beverly Ingram)Email: [email protected]

Youth FundraiserIn memory of Matthew Bailey,

Mrs. Petrucci�s Third Grade Class inGreenport, New York donated $68 inthe spirit of the holiday season.

Annual UMDF Benefit Dinnerraises more than $15,000 inOctober. Special thanks toDavid, Angela, Nicholas andBrendan Nunno for all their

HARD work!Upcoming Events:� February - Snow Tubing Event(partial proceeds to UMDF)

� May 7, 2005: Matthew DudgeonMemorial Walk (partial proceeds)

� May 21: Walk in Chatham, NJ and5K Run/Walk in North Haven, CT

Youth Fundraisers� Floral Park Memorial High School,NY, raised $130.67 in a Coins for aCure campaign in honor of NicoleKelli Nieves.

� In Honor of Brittany Berry, kids atCordello Avenue School in CentralIslip, NY, raised $345 by having aUMDF Day. Each child wore greenand was given a chance to win anice cream party. Special Thanks to all the children

and youth who participated inthese events. Your donations

can and will Make a Difference!

Special Thanks� Barbara Howard of Mansfield,MA, went door-to-door andcollected money for UMDF inhonor of Ryan Shea, son of Deband Bill Shea.

� Mary Ryan hosted an Evening ofJewelry in honor of her son,William Ryan, and raised $300.

Pictured Above: Emily & Jackie Tyler,Heidi Bailey, Darlene & Natalie Tongue,

and Betel & Billy Arnold

The Longmeadow, MA, Mito-What? 5K Run/Walk was heldon October 3, 2004 and raised

more than $37,800! Great work,New England!

In lieu of wedding favors, Aimee andKevin Beam donated $500 to UMDF

in honor of their flower girl, KaylaBiagiotti. Thanks Aimee and Kevin -

enjoy your new life together!!!

Volunteers braved the rain inSeptember during the New England AirShow at Westover Air Reserve Base inChicopee, MA. $900 was donated toUMDF in honor of the Ingram Family.

!! Special Welcome to !!UMDF�s Newest Chapter

ATLANTA AREACHAPTERAtlanta, GAPresident: Holly CappPhone: 770-506-7441 Email: [email protected]

Holly Capp, President Ashley DiLorenzo, Vice PresidentKatie Lyons, TreasurerMary Swinn, Secretary

The Atlanta Area Chapterofficially joined the ranks thispast Fall and their officers are:

1st Annual Fore-a-Cure GolfTournament was a HUGE

Success - raising more than$40,000 in November. Well done!

The Atlanta Chapter celebratedthe holidays together and enjoyed

a visit from Santa


DELAWARE VALLEYCHAPTERPhiladelphia, PAPresident: Maripat ShellyPhone: 215-256-0273Email: [email protected]

INDIANA CHAPTERIndianapolis, INPresident: Sue Ann BubePhone: 317-894-9099Email: [email protected]

Upcoming EventPack The House

The Chapter is once againworking together with a local hockeyteam, the Indiana Ice, for a victoryagainst mitochondrial disease! Anyperson or company that purchases atleast 30 tickets will have the chanceto win two courtside Pacers tickets.The event will be held at ConsecoFieldhouse on February 12th at 7:00p.m.Coins for a Cure

Blue River Valley Schools, ofMount Summit, IN, raised $1,100 inhonor of Seth Boling.

�After coming back from thePittsburgh UMDF conference, wedecided to do a Coins for a Cure inour children�s school. Our hopes andprayers are that many other schoolswill do this and together we will finda cure.� - The Boling Family

Upcoming Events:� 6th Annual Energy for LifeRun/Walk (formerly Shelly�sHeroes) -- Tentatively scheduled forMay 7, 2005 (Check www.umdf.org).

� June 11, 2005 - Brew at the Zoo,Elmwood Park Zoo.

� Dodge for a Cure - DodgeballTournament for participants 18years and over. Date and locationTBA.

� COOKBOOKS - contact thechapter to order your cookbooktoday. $15.00 mailed anywhere!

Successful Events� DJs, 9 to 5, raised $100 during afundraiser in September.

� You Go Girl raised close to $4,400to benefit UMDF. Special thanks toJoe & Happy Halligan and KevinLawn.

� The chapter Fashion Show was alsoa success - raising close to $5,775in November. Special thanks to thePolsky Family!

Chapter Activities

Holiday Party Always FUN!The chapter�s annual holiday

party at Merion Tribute House wasfilled with happy families doingcrafts, enjoying magic and animpromptu talent show. Picturedabove, the DiPietro boys show offtheir singing talents. Crystal Beaded Bracelets

Beautiful crystal beadedbracelets are now available throughthe chapter. You can choosebetween three sterling silvermessages (Hope, Miracles, Cure)or a single message (Hope). Allbracelets have the awarenessribbon near the clasp. Pictures andorder forms are available on theDelaware Valley Chapter web pageat www.umdf.org.

Special thanks to Beth Hartmanfor starting this wonderfulfundraiser to benefit UMDF.

KANSAS CITY CHAPTERKansas City, MOPresident: Pam JohnsonPhone: 913-631-3070Email: [email protected]

Save the DATEKansas City Chapter's Second

Annual "Mito What?" 5K Runand 1 mile walk is set forSaturday, May 14, 2005. The eventwill be held in Corporate WoodsFounders Park. Please contactDeidra Atchley at 816-537-6293for more information and find outhow you can help make this eventa success once again!!

ARIZONA CHAPTERPhoenix, AZPresident: Suzanne PerrymanPhone: 480-419-0167 Email: [email protected]

Suzanne Perryman, President Courtney Whynott, Vice PresidentMarge Calabrese, TreasurerJanet Churchward, SecretaryThom Montgomery, New Member Committee Chair

The new officers have been busyplanning meetings and events for2005 and beyond. A Family &Friends Educational Day is one

event in the works for thisrevitalized chapter!

!! UMDF Welcomes !!Arizona�s New Officers

� Anytime Women�s Workout raised $100 inhonor of Anne and Alexandra Churchward.Thanks, Karen Fisch Hidalgo!

Special Thanks to:


SOUTHERN CALIFORNIA CHAPTERLakewood, CAPresident: Linda CooperPhone: 714-921-2324 Email: [email protected]

New Leadership Positions!The Chapter has reorganized for

2005, and new officers have beenassigned. The new officers are:

Thank you all for your ongoingcommitment and for accepting yournew positions.

Thankful HeartsLooking back to 2004, the

Chapter would like to thank all thefamily, friends, neighbors,coworkers, and communities for allof their support and help with theUMDF mission and our fundraisingefforts. A great big THANK YOUto Alison DeVriendt and LauraMaese for making the 2004 WineTasting event so successful in May.Bob and Linda Cooper's family,friends, and co-workers at Smith-Cooper International raised$3,500.00 for the UMDF as an endof the year holiday gift for them.What a great way to end 2004, withkindness and thanksgiving.Upcoming Events

Visit www.umdf.org for dates andlocations for the Chapter WineTasting Event and the Chapter GolfOuting.

Chapter ActivitiesOHIO CHAPTERCleveland, OHPresident: Jennifer LymanPhone: 330-929-4430Email: [email protected]

Upcoming Events� March 5 - 2nd Annual �Bet on

Baylee� Casino Night atRoseville Community Center(near Zanesville, OH)

� May 29 - Shadow Woodstock2005 - an outdoor jamboree, andfamily fun event at 9911 ShadowWood Circle, Chagrin Falls, Ohio44023 at 4:00pm. For moreinformation, please contact JohnKobunski at 440-479-2371.

� June 4 - Fourth AnnualKFC/UMDF 5K Run/Walk,Forest Hills Park in ClevelandHeights, Ohio. Please visitwww.umdfohio.org for moreinformation!

Special Thanks� The Big Bear Farms (BBF)

neighborhood raised $850 inhonor of Ellie Kovalcik duringtheir annual hayride and bonfire.

� Park Road Bar & Grill raised$124 in honor of Emily Pleskoduring a coins campaign.

Hope BraceletsThe Ohio Chapter is selling

bracelets with custom-made,sterling silver beads, large cube,and round Swarovski crystals. It iscompleted with a large silver heartcharm with HOPE engraved onboth sides near clasp.

For ordering information,contact Melissa Nadja at La�Jules440-937-9947. Picture of thebracelet is available online on thechapter webpage at www.umdf.org.

� Frank and Paul Melison, of NewImage Haircutters in Willowick,OH, held several hair cut-a-thonsthis summer during the LakeCounty Captains baseball games.These wonderful cutters raised$745.67 in honor of JonathanKucaric.

Energy for Life Campaigns� Mary Ann Donut Shoppe, Inc.

raised $470 in honor of AmandaWelden.

� In honor of Dori Anne Szelesta,Thomas Wiedt sent in $150.

Second Annual Family Spaghetti Dinner in Mentor, OH

Hosted by the Arnold andKeeney Families on January 8, thedinner raised more than $6,200 inhonor of Maiya Keeney and themany other individuals affected bymitochondrial disease. Keep up thegreat work!

Linda Cooper, President Alison DeVriendt, TreasurerLaura Maese, Fundraising ChairTia Acosta, Membership ChairDebi Connelley, Meetings Chair

Take me Out to the Ballgameand Get a Haircut to Benefit

UMDFNew Image Haircutters, of

Willowick, Ohio, will onceagain hold a cut-a-thon during

the following Lake CountyCaptains games:

Friday, May 20, 2005Friday, June 17, 2005Friday, July 29, 2005

Friday, August 12, 2005Friday, September 2, 2005

If you would like tovolunteer to help hand out

information about UMDF andMitochondrial Disease, please

contact the chapter.

Want to Get Involved?!!Contact your local chapter orgroup today. Chapters andGroups will continue to growwith your HELP. YOU can

make a difference!


Action RequiredA Donor is Waiting . . . And It�s Up to You

UMDF Development Corner

Bulletin!!Several major companies are ready to provide funds

that can be donated to UMDF - and you can have thededuction.

Money is waiting, and only you can make it happen.In fact, securing these funds for UMDF's work couldactually save you money.

Is there any reason that you can say "No" to someoneelse providing you with money to give to UMDF and thefight against mitochondrial disease? Is there any reasonyou would say "No" if it meant more money in yourpocket, or a larger balance in your retirement account?

The "Catch"?You'd have to allow world-class money management

firms and portfolio managers to work with yourretirement assets.

100% of your money goes to work from Day 1, withno up-front sales charges, in your choice of investmentvehicles from America's leading fund families andmanagers. And you can actually get more dollars intoyour individual retirement account�even if you'realready making the maximum contribution�more dollarsto grow and to compound tax-free until you access them!

You could be eligible for one of these programs, if youfit into any of the following scenarios: � If you have retirement money in an IRA, mutual

funds, a retirement annuity, a 403 (b) plan or aqualified plan that allows in-service distributions;

� If you have recently retired or left the employ of acompany with a vested balance in their plan;

� If you are a business owner, or have a professionalpracticeThere are a great many choices, advantages, caveats,

restrictions and requirements that you should be aware of.UMDF has experts on hand to explain how it works inyour particular case.

Here's an example:John is a 54-year-old professional in the 35% tax

bracket, and plans to retire at age 65. He has $90,000in his IRA, and makes the maximum contribution eachyear; he also has $100,000 in mutual funds and willinvest an additional $10,000 this year.

If John follows this plan and makes a $3,500 IRAcontribution for 2004, he would have a $93,500 balancein his IRA and $110,000 in mutual funds, for a total of$203,500 between the two, plus or minus marketperformance.

But John actively supports the UMDF. He makes hiscontribution and then elects to roll over his IRA to oneof the companies offering the program. John receives abonus of 4%, or $3,740, bringing his IRA balance to$97,240.

John then takes $3,740 from the $10,000 earmarkedfor investment, the amount of his bonus IRA credit, anddonates it to UMDF. This charitable contribution, inthe 35% tax bracket, yields a tax savings of $1,309. Heinvests the $6,260 remainder and the $1,309 taxsavings in his mutual funds.

John now has $97,240 plus $107,569 for a total of$204,809 (vs. $203,500) - after sending $3,740 toUMDF. And more of his money is in the taxadvantaged IRA!

Could you help? Money is waiting, money you can contribute, if only

you'll agree to learn more about it. Call the UMDFoffice today, and we'll get you all the information, withno strings attached. It is within your power to providehelp�meaningful help�now. Don't let thisopportunity slip away.

Mitochondrial Disease Benefit Concert

Saturday April 2, 2005Hamilton Place Studio Theatre,

Ontario, CanadaFor more information,

Call Andy McDonald at 905-524-1951or email [email protected]

Proceeds benefit mitochondrial disease efforts in Canada.

Newsletter Correction New England Chapter

The Walk to Create Awareness inNorth Haven, CT was organizedin honor of Mary and MatthewPisani�s son, Nicholas Pisani -

not Matthew.

Carry American Express?You can donate to UMDF throughthe American Express Donation

Site(www.americanexpress.com/give)which is powered by JustGive.org.

To date, UMDF has received$48.88!


United Mitochondrial Disease Foundation Mitochondrial Medicine 2005Gateway to a CureThe Scientific Topics and Speakers

Day 1: Wednesday, June 15, 2005Platform Session 1: Regulation of MitochondrialFunction� Regulation of Mitochondrial Function by Post-

translational Modification, Roderick Capaldi, PhD� Ethylmalonic Aciduria: a Marker of Mitochondrial

Stress? Niels Gregersen, PhD

Platform Session 2: Epidemiology ofMitochondrial Disease� Epidemiology of Primary Mitochondrial Disorders,

Patrick F. Chinnery, PhD, MRCP� Epidemiology of Environmental and Acquired

Mitochondrial Disorders, William C. Copeland, PhD� Acquired Mitochondrial Disease and HIV Drugs, Grace

McComsey, MD

Day 2: Thursday, June 16, 2005Platform Session 3: Mitochondrial and NuclearCommunications � PGC-1a: A Versatile Integrator of the Mitochondrial

Biogenic Program, Daniel P. Kelly, MD� The Retrograde Response: How and Why

Mitochondria Talk to the Nucleus, Ron A. Butow, PhD� Fatty Acids, Nuclear Factors, and Biogenesis, Deborah

G. Murdock, PhD

Platform Session 4: Mitochondrial Disease andAnesthesia� Mitochondrial Disease: Anesthetic Considerations in the

Preoperative Period and Intraoperative Concerns,Joseph Farlo, MD

� C. Elegans Mitochondrial Function--Can Worms be aModel for Humans? Margaret Sedensky, MD

� Anesthetics and Mitochondrial Patients, Phil Morgan, MD

Day 3: Friday, June 17, 2005Platform Session 5: Diabetes and MitoDysfunction� Mitochondrial Defects in Type 2 Diabetes, Gerald I.

Shulman, MD, PhD � Mitochondrial Dysfunction in the Diabetic Heart, Daniel

P. Kelly, MD

Platform Session 6: Gene Targeted Therapiesand Mitochondrial Disorders� Clinical Aspects & Gene Therapy of Leber Hereditary

Optic Neuropathy, John R. Guy, MD and Alfred S. Lewin, PhD

� Development of Mitochondrial Gene ReplacementTherapies, James P. Bennett, Jr., PhD

� Approaches to Mitochondrial Gene Therapy, VolkmarWeissig, PhD

� Banquet Keynote: Douglas C. Wallace, PhD

Day 4: Clinical Program Saturday, June 18, 2005Clinical Session (For Physicians andFamilies) - Morning� Introduction to Mitochondrial Disease, Douglas C.

Wallace, PhD� Ophthalmology and Mitochondrial Disease, John R.

Guy, MD� Why do Viral Infections Cause Setbacks in

Mitochondrial Disease? Robert K. Naviaux, MD� Cardiac PET Imaging: Application in Mitochondrial

Disease, Robert J. Gropler, MD

Clinical Session (For Physicians andFamilies) - Afternoon� Symptom Management in Mitochondrial Disorders,

Bruce H. Cohen, MD� Mitochondrial Patients Having Anesthesia, What to

Expect? Phil Morgan, MD� Coenzyme Q10 and Mitochondrial Disease, Richard

H. Haas, MB, BChir

Meet us in St. Louis!MitochondrialMedicine 2005Gateway to a CureJune 15-18, 2005

Hyatt Regency St. Louis atUnion Station


atewayto a CCureG Family Meetings

Friday, June 17, 2005Morning Sessions� Working with Volunteers� UMDF Present and Future - Ask the Trustee� Funding the Cure� Insurance Issues� Living with Mitochondrial DiseaseAfternoon Sessions� Mito Basics for the Newly Diagnosed

John Shoffner, MD� Diabetes and the Mitochondrial Adult Patient

Douglas C. Wallace, PhD� Therapeutics and Nutrition

Richard H. Haas, MB, BChir

Saturday, June 18, 2005� Ask the Mito Doc Panel: John Shoffner, MD;

Richard Haas, MB, BChir; Russell Saneto, DO;and David Whiteman, MD

� UMDF Funded Research - Hear ProgressReports from the Bench

� Genetics and Mitochondrial Disease, SusanWinter, MD

� What to Expect as we Age with MitochondrialDisease, Douglas Wallace, PhD

� Management Strategy for Acute Illness inPatients with Mitochondrial Disease, RussellSaneto, DO

! Networking room gives families a designatedspot to meet and share experiences.

! The �Doctor is In� booth is a favorite amongpast attendees and will be back for 2005.Attendees speak one-on-one with topspecialists.

! UMDF presents grant money tomitochondrial researchers and families hearprogress reports from past projects funded byUMDF. $1 million will be awarded in 2005!

Beginning in 2003, Morgan�s Foods Inc., basedout of Beachwood, Ohio, graciously placed coin

collection banks in Kentucky Fried Chicken (KFC)restaurants across Western Pennsylvania.

These wonderful KFC franchises have raisedmore than $20,000 to benefit UMDF.

On behalf of all our UMDF families and friends,thank you Morgan�s Foods for helping us RedefineHOPE for those battling mitochondrial disease and

giving them the Energy for LIFE!

Thanks to Tom Arnold, grandfather to BobbyArnold, Premier Restaurant Management

Company's Kentucky Fried Chicken franchises havealso been busy collecting coins to benefit UMDF.

More than $5,400 has been donated to UMDF sinceMay of 2003. The coin collectors ask patrons to

"Donate your change and help UMDF find a CUREfor Mitochondrial Disease!" Tom also introduced

UMDF to Morgan�s Foods andPremier Restaurant/KFC is the title sponsor for

the Ohio Run/Walk - donating $10K annually to helpUMDF move One Step Closer to a Cure!

Premier RestaurantManagement

Company

Your Continued Support is Pr iceless!! !

Special Thanks to

Registration Brochures will be mailed to UMDF members and physicians in February. If youdo not receive a brochure, please email [email protected] to get on our mailing list.

The brochures will also be available online at www.umdf.org.


we eat, are stored on a molecule called NADH. MRCproteins and the chemical reactions they perform arehighly conserved among simple and complex animals.When conserved proteins are found in manyorganisms, investigators will often choose to use anon-human or even a non-animal model system thatsimplifies or accelerates experiments and theacquisition of knowledge. A Worm Model System

Caenorhabditis elegans, a free-living worm ornematode, is one of the simplest known animals (Fig.2). Using this worm as a model system offers severalkey experimental advantages: the worm is simple in itsanatomy and genome, it is transparent, it is easy togrow in the lab, it has a short life cycle, and it is wellsuited to genetic analysis. The worm's native habitatis in soil, especially decomposing vegetation, where itfeeds on microbes. C. elegans is of no directeconomic importance to man and yet it is one of themost studied animals in science. Adult worms areabout 1 millimeter (1/25th of an inch) in length. C.elegans worms usually reproduce as hermaphrodites;

they produce both eggs and sperm and a newgeneration of 250-300 progeny are born every 3-4days. Through genetic manipulation, it is possible toestablish specific C. elegans lines or strains in whichthe progeny are all genetically identical, havinginherited both the maternal and paternal genes fromthe hermaphrodite. Thus, millions of geneticallyidentical animals can be cultured for biochemical orother analyses in a very short time.

C. elegans is physically a very simple animal;when an egg hatches, the first stage larva has exactly558 cells. The number of cells increases as eachworm develops through 4 larval stages into the adulthermaphrodite, to a final total of 959 non-reproductive cells. For comparison, a tadpole hasabout 1 million cells. Each adult hermaphroditecontains 302 nerve cells (some of which serve as aprimitive brain), 95 body muscle cells, 20 pharyngealmuscle cells (the pharynx is a mouth-like organinvolved in grinding and pumping food beforesending it into the intestine), and other cells thatform defined tissue types. Worms have specificbehaviors such as being attracted to or repelled by

Worms with Mitochondrial DiseasesContinued from page 1

Figure 1: Cytochrome b2-Mediated NADH Oxidation

Complex I Complex III Complex IVQ cyt c

! "#NAD+

NADH

O2

2H2O

! ! !

$%

digestion offats, proteins,carbohydrates

&

NADH

NAD+ "lactatedehydrogenase

"" lactate

pyruvate

""GeneTherapy

Q: ubiquinonecyt c: cytochrome c


CYB2CYB2

Figure 2


Mustache for Kids - RaisesMore than $1,400

This unique event began onNovember 17 in Columbus, Ohio,by Carson Roger�s uncle, DarrenMeyer. Carson lives in Greer, SC.For four weeks, Darren�s co-workers participated in a mustachegrowing competition anddonations were collected.

Weekly updates were emailed tothe UMDF national office to showthe progress of the growing

�staches. A variety of awards weregiven to competitors: Rockin�estMustache, The Chef Boyardee, andBest in Show/Sweetest �Stache of2004 were just a few.

The sister of one of thecompetitors mentioned thecampaign to her class and thestudents joined the fun by holdingtheir own competition. With thehelp of markers and a little make-up, these middle schoolers raisedalmost $400.

Thank you to all employees atMSI Design and to WatkinsMiddle School in Pataskala, Ohio!What a Blast!!!

!! More UMDF !!Fundraising Stars

� Coins for a Cure - In honor ofAsher Gould - $277.55. ThanksCarol�s Kitchen of Boca Raton,FL.

� 2004 2nd Annual Crop for Carson(Rogers) in Greer, SC - $1,418.75.

� 2004 Energy for Life in honor ofRiley Peek - $319.50. Thank youRBC Centura Bank of Palmetto,GA.

� 2004 Entertainment/Enjoy Booksraises $2,502. Way to go Ron &Donna Miklos!!!

� 2004 Season for Giving -shopping event raises $228 atMonroeville Mall, PA.

� Angelica & UMDF Golfing For aCure Outing and Angelica/UMDFFamily Fun Day raised a total of$3,886.74 in Cypress, TX.Thanks Cynthia!

� The Crespi Mothers Golf Clubdonated $100 in memory of CodyBracken.

� In lieu of gifts for her 10thBirthday, McKinsi Thompsondonated $300 to benefit UMDF!

� Misty Brown, mother to Abigailand Mikaela, is a Mary Kayconsultant and has pledged todonate 10% of every sale shemakes to UMDF. So far, she hasdonated $100 - BEAUTIFUL!!!

� James Lomeo, Mayor ofMonroeville, PA, performswedding ceremonies and variousother mayoral duties. In lieu of hisfee, he has asked individuals todonate to UMDF. Thanks Jim!!!

Fundraisers

The 4th Annual Mito-What?Margaritaville Cruise raised

$3,000 on August 27 in honor ofMorgan Kozuch. Pictured above -Morgan with Michigan firefighterKarey Prieur, who won the $500

cash prize and graciously donatedit back to the Foundation. What aguy! Next year�s Cruise is set for

August 17, 2005!

Thanks Kozuch Family!!!

The First Annual 5K Walk inAlabama raised more than

$34,193.75 on October 9, 2004. AnnWashburn, of Birmingham, organizedthe event with the help of family andfriends to honor the memory of her

son, Brock. Pictured above are Ann�sidentical twin nieces who were

enjoying the day!

In Memory of Noah Moore,Aker Kvaerner of Pittsburghchose UMDF as the recipientof their 2nd Annual Chinese

Auction for Charity.Employees raised more than$7,900 in memory of Noah.Thank YOU Aker Kvaerner

employees!

T H A N K S


� Emily Kusuhara (pictured left withRiki), of Japan, loves her brother somuch that she donated most of hersavings to UMDF in honor of Riki�s 6thBirthday. Emily & her friends donated$200 - what a gift!

� Candy machines continue to raisemoney and awareness in Mohan�sRestaurant, RibKens, Pennzoil andLaCava�s Italian Market - $444.06.Thanks Chuck!

� D Morgans Restaurant raised $307during a Fine Arts Festival in honor ofSherry Mathis in Cartersville, GA.

� Rib-Kens Restaurant in Monroeville,PA collects coins and donated$111.11 its first quarter.

� Cans for Ashley raised $387.50 in2004. Thanks Randy, Sandi andAshley!

� UMDF Staff paid $5 each to �dressdown� in memory of Gina MarieMohan on January 20 and raised $40.

� Heartbeats for Mito event in theUniversity Mall, Tuscaloosa, Alabamaraises $713 in October. Great jobAnn Eide!

Thank YOU to more of our !! Fundraising Stars !!

HELP! We Need your Jewish Holiday

Recipes13-year-old Hannah Roberts,

from Canton, Ohio, is workingon a Jewish Holiday Cookbookfor her Bat Mitzvah. The moneywill go to UMDF to help usmove One Step Closer to a Cure.Please send Jewish HolidayRecipes to 1253 LinwoodAvenue SW, North Canton, OH44720. Deadline to submitrecipes is May 31, 2005.

FundraisersMeetThe UMDF Board

Bruce H. Cohen, MDCleveland, Ohio

Dr. Cohen joined the UMDFBoard in 1998. He has chaired theChapter Committee, serves on theExecutive Committee and presentlychairs the Symposium Committee.Gerald A. Cook, Esq.Pittsburgh, PA

Mr. Cook joined the UMDF Boardin 2004 and serves on the Program/Policy Committee. He has alsoserved as legal counsel in the past.Stan Davis, TreasurerPepper Pike, Ohio

Mr. Davis joined the UMDF Boardin 2001, and currently chairs theFinance Committee, which analyzesUMDF's investment strategies. John A. DiCecco, ViceChairmanApollo, Pennsylvania

Mr. DiCecco served as BoardTreasurer from 1998 to 2003, guidingUMDF in developing its financialpolicies and systems. He currentlychairs the Governance Committee.Charles L. Hoppel, MDCleveland, Ohio

Dr. Hoppel joined the UMDFBoard in 2002, bringing theperspective of medical researcher tothe Board. Presently, Dr. Hoppelchairs the Research and SABRestructuring Subcommittees.Richard W. Kubach, Jr.Newtown Square, Pennsylvania

Mr. Kubach was appointed to theUMDF Board in November 2003 andchairs the Planning/MarketingCommittee. Charles A. Mohan, Jr.,Chairman Monroeville, Pennsylvania

Mr. Mohan helped found UMDFin 1996, and has served as BoardChairman since its inception. Hechairs the Executive Committee andappoints committee chairs.

Mary PisaniNorth Haven, Connecticut

Mrs. Pisani was appointed to theUMDF Board in 2004 as the newChapter Liaison and also serves asthe President of the New York MetroChapter of UMDF. She currentlychairs the Chapter Committee.Joseph RiceSaint James, New York

Mr. Rice was appointed to theUMDF Board in November 2003and helped found the UMDF NewYork Metro Chapter and chairs theHuman Resources Committee.Nick Rillo, SecretaryChicago, Illinois

Mr. Rillo has served on theUMDF Board since 1996. He has

chairs the IT Committee and providesvaluable insight on technicalconcerns. Sharon ShawCave Creek, Arizona

Ms. Shaw was appointed to theUMDF Board in November 2003 andalso served as President of theSouthern California Chapter ofUMDF for three years, stepping downin 2003. Ms. Shaw also serves on theSymposium Committee.W. Dan Wright Vernon, TX

Mr. Wright joined the UMDFBoard in 2004 to complete RandWortman's term. He currently chairsthe Search Subcommittee for the newExecutive Director.

� Connelle Salon of Boca Raton,FL held a raffle in honor ofAsher Gould raising $3,879.50.



certain chemicals and are capable of rudimentarylearning. C. elegans is transparent, allowing for themicroscopic examination of anatomy and behavior inlive animals. The average lifespan of a worm is 2 to 3weeks; after reproducing, the worm ages, loses vigor,and finally dies.

The C. elegans genome consists of 100 million basepairs of nuclear DNA (nDNA), about 30-fold fewerbase pairs than in the human genome. Themitochondrial DNA (mtDNA), at 13,794 base pairs, isvery similar in size and gene content to human mtDNA(16,569 base pairs). Human mtDNA encodes thirteenproteins of the MRC, and twelve of these same proteinsare produced from worm mtDNA.

Although C. elegans does not have complex organssuch as a heart or a liver, its simplicity as an animal andits sophistication as an experimental model allow us toprobe the fundamental biological mechanisms thatoperate in healthy and in disease states. Even more,certain mutations related to disease would be lethal inmore complex organisms. These mutations aretolerated by worms and can thus be studied in detail.Worms With Mitochondrial Disease

Unfortunately, most mitochondrial disorders are sorare that the relationships between mitochondrialmutations and disease mechanisms remain poorlyunderstood. The MRC provides the majority of a cell'senergy requirements, and at first glance, it might beexpected that mitochondrial diseases are manifestationsof energy shortages. The diversity of symptoms andcomplexity of multisystemic mitochondrial diseasesargues against a simple energy shortage model. Ourworm model system is proving useful in identifyingadditional, non-energy related mechanisms by whichmitochondrial dysfunction impairs normal cell function.We have identified at least three pathologicalmechanisms that contribute to disease: lactic acidosis (ametabolic imbalance related to excess NADH),impaired assembly or function of MRC proteincomplexes not directly affected by a mutation, and theproduction of reactive oxygen species.

We are focussing our work on mitochondrial diseasecaused by defects in complex I. Complex I is the firstand largest of the MRC proteins and is responsible forthe capture of energy from the high-energy electronsstored on NADH molecules. The C. elegans genecalled nuo-1 is the source of one component of complexI, the protein subunit that recognizes and binds NADH.The NUO-1 protein is the worm equivalent of thehuman 51-kilodalton protein (produced from the humanNDUFV1 gene). The worm NUO-1 protein and thehuman 51-kilodalton protein share about 75% identical

amino acids, a strong indication that their functions arevery similar in both organisms. When both copies ofthe worm nuo-1 gene harbor a severe mutation, mutantanimals begin early development normally but arrest inthe third larval stage and remain at this juvenile stagefor the remainder of their lives. This arresteddevelopment highlights the importance of normalcomplex I and MRC function for development,maturation, and reproduction in C. elegans.

Mutations affecting a single MRC protein areresponsible for some mitochondrial diseases in humans(see Table 1). We can use our worm model system tostudy the effects of such mutations on the analogousMRC proteins in worms. To better understand howhuman complex I mutations can produce disease, weintroduced three reported mutations in the humanNDUFV1gene into the C. elegans nuo-1 gene. Each ofthese mutations modifies only one amino acid of theprotein and is believed to reduce complex I activity butnot to completely inactivate it. All three mutationsaffect amino acids conserved between the worm andhuman proteins; conserved amino acids are more oftenimportant for protein function.

Each mutated nuo-1 gene was introduced into C.elegans hermaphrodites and offspring carrying thesegenes were isolated. The three mutated NUO-1proteins were produced in the corresponding offspringand incorporated into complex I of the offspring.Compared to the worms with a normal NUO-1 protein,the mutated proteins led to significantly lower complexI activities. Although the mutated proteins allowsufficient energy production for development andreproduction to proceed, the worms display reducedfitness. We measure fitness by determining broodsizes (total number of offspring per hermaphrodite)and lifespans. Worms carrying the mutated proteinsalso show reduced levels of respiration (oxygenconsumption) and signs of premature aging, such asmuscle degeneration.

In the worm models for human disease-causingmutations of complex I, we have identified at leastthree molecular mechanisms that are contributing tothe disease phenotype or symptoms:� Worms carrying the T434M, A352V, and A443F

mutations (Table 1) all had significantly elevatedlevels of lactate. Lactic acidosis can occur whenMRC function is impaired. NADH accumulatesand is diverted towards the formation of lactic acid(lactate, Fig. 1). In humans, excess lactate canproduce malaise, muscle weakness, exerciseintolerance, and vomiting. It may also contribute to



long-term mitochondrial disease progression byaffecting the production of other proteins related toenergy metabolism.

� Our worms with mutations in complex I proteinssuffered from a deficiency in complex IV, theenzyme that transfers electrons from the MRC tooxygen to form water (Fig. 1). Complex IV proteinlevels as well as activity levels were significantlyreduced in worms with complex I mutations,suggesting that complexes I and IV are in some wayinterdependent. Impaired complex IV activity likelyexacerbates energy shortages and lactic acidosis.

� Finally, we noted that our nuo-1 mutant worms arehypersensitive to oxidative stress, which results inelevated levels of damaging reactive oxygen species.The hypersensitivity can be attenuated by sodiumdichloroacetate or by riboflavin. Furthermore, boththe A352V and the A443F mutants show improvedfitness when supplemented with ascorbate, a reactiveoxygen species scavenger. Rather than efficientlyharnessing the energy in NADH for the synthesis ofATP, mutant forms of complex I leak high-energyelectrons to oxygen, forming reactive oxygenspecies. These results suggest that mutated complexI produces damaging reactive oxygen species that

may contribute to the premature aging anddiminished lifespans of the mutant worms.

Molecular Mechanisms and TherapiesSome forms of mitochondrial disease can be

improved by pharmacological agents such as vitamins.We have tested the response of the mutant worms inour model system to some of these agents. The goal ofthis part of our research is to determine how suchpharmacological agents influence the molecularmechanisms of mitochondrial disease. � Riboflavin supplementation significantly increased

brood sizes in all three types of mutant worms.Interestingly, the riboflavin reduced observed levelsof lactate in the A443F mutant, but not in the othertwo mutants.

� Thiamine supplementation increased brood sizes inthe A352V mutant.

� Sodium dichloroacetate (an activator of the pyruvatedehydrogenase complex) increased the brood sizesof the A352V and the A443F mutants. It alsomarkedly reduced their lactate levels. Because thebeneficial effects of riboflavin on the A352V mutantare not associated with reduced lactate levels, wesuggest that the mechanisms of action for sodium

Table 1


Human Human C. elegans C. elegansMutations Disease Mutations DiseaseT423M/R59X � vomiting T434M � moderate reduction in brood sizecompound � progressive muscular hypotonia � moderate decrease in lifespanheterozygotes � myoclonic epilepsy � modest signs of premature aging

� psychomotor regression � moderate drop in respiration� lactic acidosis � moderate lactic acidosis� death at 14 and 17 months � hypersensitive to oxidative stress

� responsive to riboflavinA341V � myoclonic epilepsy A352V � severe reduction in brood size

� muscular hypotonia � severe decrease in lifespan� psychomotor regression � severe premature aging� macrocephaly � severe drop in respiration� elevated CSF lactate � moderate lactic acidosis� patient, age 10, is blind and � complex IV deficiency

severely spastic � hypersensitive to oxidative stress� responsive to riboflavin, sodium

dichloroacetate, ascorbate, thiamineA432P/2base � vomiting A443F � severe reduction in brood sizepair deletion � hypotonia � severe decrease in lifespancompound � lethargy � severe premature aging

� severe drop in respirationheterozygote � apnea � severe lactic acidosis

� lactic acidosis � complex IV deficiency� death at 18 months of metabolic � hypersensitive to oxidative stress

acidosis � responsive to riboflavin, sodium dichloroacetate, ascorbate.


dichloroacetate and riboflavin aredifferent.Our results indicate that lactic

acidosis is responsible for at leastsome of the pathogenic effects ofcomplex I mutations, but clearlyother mechanisms also play a rolein these diseases.

Gene therapy involves theintroduction of foreign genes toreplace or compensate for missingor damaged genes. Gene therapyoffers the possibility of a cure or ofproviding a long term treatment inmany diseases. Gene therapy forcomplex I dysfunction ischallenging because of the largenumber of genes needed toassemble complex I (~37 nuclearand 7 mitochondrial genes).Furthermore, the mtDNA is notcurrently accessible for such geneticmanipulation.

We are investigating the use ofgene therapy as a means ofcompensating for the loss ofcomplex I activity by moderatingthe effects of lactic acidosis. Onepossible route to this goal is theintroduction of a new enzyme intothe equation. The yeast enzymecytochrome b2 (CYB2) is amitochondrial enzyme; CYB2-likeenzymes are not found in mammalsor in nematodes. CYB2 convertslactate to pyruvate and reducescytochrome c (Fig. 1). The pyruvateis re-converted to lactate by anendogenous lactate dehydrogenase,using up NADH in the process.The net result of the CYB2 andlactate dehydrogenase reactions isthe reduction of 2 molecules ofcytochrome c and the conversion of1 NADH to NAD+. The reducedcytochrome c molecules provideelectrons to complex IV in thenormal functioning of the MRC,and the complex IV reactioncontributes to ATP synthesis inmitochondria. Thus, the addedpresence of CYB2 in mammals andworms should lower lactate and

NADH levels while contributing toATP synthesis.

We have expressed the CYB2gene in the more severe A352V andA443F complex I mutants. WithCYB2 active in the worms, mutantbrood sizes are increased 150-225%. Lifespans are lengthened byalmost one third and respirationrates are stimulated from 40-50% ofnormal levels in the mutants to 85-90% of normal levels with CYB2expression. To further documentthe effects of CYB2, we aremeasuring the levels of CYB2protein and activity present inisolated worm mitochondria. Wealso predict that CYB2 expressionwill significantly decrease lactatelevels and sensitivity to oxidativestress. We believe that thebeneficial effects of CYB2expression are directly due toreductions in lactate and NADHlevels.

In conclusion, the significantlyimproved fitness of CYB2-expressing mitochondrial mutantssuggests that lactic acidosis isresponsible for much of the severityof complex I-associated disease.The development of therapies ortreatments that address metabolicacidosis may prove most beneficialin moderating the pathologicaleffects of MRC dysfunction. In thelonger term, gene therapyapproaches that directly target lacticacidosis in the worm may also beadapted to provide long termclinical benefits to those that sufferfrom mitochondrial dysfunction.


Aon Association ServicesAT&TAXA FoundationAdams, Harkness & Hill, Inc.Altria Group. Inc. (Phillip Morris

Companies, Inc.)American Refining Group, Inc.BD Matching Gift ProgamBank of AmericaBabson Capital Management, LLCBell SouthCNA FoundationCapital Group CompaniesChubb CorporationCrail-Johnson FoundationEOG Resources, Inc.FM Global FoundationFleetFrito-Lay (Pepsi-Cola)Gap FoundationGraingerHewlett-Packard CompanyHP FinancialKey FoundationKimberly-Clark FoundationKraft FoodsThe JP Morgan Chase FoundationJohnson & Johnson Family of

CompaniesLehman BrothersLoomis, Sayles & Company, LPMassachusetts Mutual Life Insurance

CompanyMcMasters-Carr Supply CompanyMerrill Lynch & CompanyMicrosoftNeiman Marcus GroupNewsweek (The Washington Post

Company)Nordson CorporationOppenheimer Funds, Inc.Oracle CorporationPepsiCoPfizer Inc.Rockwell International CorporationSaint-Gobain CorporationSallie MaeState Street CorporationTCF Financial CorporationTenet Healthcare FoundationTrans Union, LLCUnited Technologies CorporationWorld Reach, Inc. DBA The Charity

Giving StationYahoo, Inc.

Matching Gifts . . . Does your employer participate in

a Corporate Matching Gift Program?If so, your gift could be doubled.The following companies havematched gifts to UMDF in the past.If you or a loved one works for oneof these companies, check out thematching gift program and help usmove one step closer to a cure!!


Mito Adults CornerCalling all Mito Adults: The Mitochondrial News Needs YOU!

UMDF could use more helpers. Please consider joining the committee, submitting an article for review orsend us your experiences with a specific topic of interest. If you are willing to help, please email KaraStrittmatter at [email protected] or call 412-793-8077, ext. 106. We look forward to hearing from you!

The hassles of traveling include delayed departures,cramped quarters, and lost luggage. But for manywith mitochondrial disease, concerns about travel gofar beyond what happens when you land in Floridaand your luggage lands in the Philippines. Thismonth, adult mitochondrial patient and UMDFmember Melissa Nixon shares her advice on how tolessen the turbulence when traveling with a disability.

If flying, one of the first things to do is contact theairline's disability issues desk after getting yourreservation. "You can tell them your needs; they cantell you their rules," Nixon says. "Things are workedout way in advance so, hopefully, there are nosurprises."

It's also a good idea, she says, to check aboutseating arrangements, such as bulkhead seating,which can provide more leg (or service dog) room.Seating can be pre-reserved.

If traveling by train, it's not a bad idea to touchbase ahead of time either. There may be doorwaysthat are too narrow for wheelchairs or limited specialseating for the disabled. It's good to know in advance.

Make sure there are necessary accommodations forany equipment you need. BIPAP (Bilevel PositiveAirway Pressure) and CPAP (Continuous PositiveAirway Pressure) machines can be plugged intoairplanes, but on trains, hook up isn't guaranteed.Because of this, Nixon was once left eating the costof a nonrefundable ticket.

"It would have been a far worse disaster to get onthe train, start the trek, and then discover I could notget power for the BIPAP and was in respiratoryfailure," she says.

Airlines are required to provide oxygen, givennotice, but generally charge $50 per leg of travel.Since you won't be traveling with your own oxygen,make arrangements with the supplier to have freshtanks waiting at your destination. Decide what willwork best for your needs, such as meeting thesupplier at the airport or having the tanks set up inyour hotel room before you arrive.

Another suggestion by Nixon is in regard tomedications. It is better to keep medications in theiroriginal prescription bottles in carry-on luggage. Pillsloaded into containers other than their originalprescription containers may be confiscated, and onemost definitely does not want to lose his/her meds.

Though Nixon has heard horror stories of travelingwith Jazzy Chairs, including dissected batteries anddropped chairs. She says some folding wheelchairscan travel well by plane. However, there are noguarantees that your chair will be allowed in thepassenger area on any given flight. With a cooperativecrew, your folding chair may be stashed in thepassenger closet.

"It's less likely to be roughly handled or dissectedsince it's always in your line of vision," Nixon said."Storing a chair nearby can also make for easydisembarking."

Though airport security tightened in the wake of9/11, Nixon says initially airport screeners "for themost part, bent over backwards not to offend thedisabled." Now, the attitudes are changing.Wheelchair cushions are inspected; canes andwalkers, x-rayed; walkingsticks, forbidden. Evenservice dogs can besearched.

"I have no objection tothis," Nixon says. "My dogis properly trained, and Iwant any lurking bad guysto understand that the dog'saccoutrements are going tobe inspected."

If traveling with a service dog, Nixon suggests thatyou arrive at least one hour earlier than you would ifyou weren't traveling with one. Anyone traveling toEurope with a service dog will need to check on thenew dog passport system recently started there.

Sometimes, even the best laid travel plans can goawry. Even good can come from these situations . . .at least in a way. Nixon once had to take a city bus toa hospital. A bus driver wouldn't let her get onbecause the wheelchair lift would have to be loweredtwice, once for Nixon and the wheelchair and anothertime for her oxygen tanks and suitcase.

"A wonderfully kind young man saw whathappened," she says. "When the next bus came hemade sure I got on that bus-suitcase, oxygen tanks,and all-and then he stayed with me through a coupleof transfers all the way to the reception desk of thehospital."

"I was so sick I was put straight into cardiac ICU,"she says, "but I will always remember my tall coolangel with the gorgeous basketball shoes."

Mito Adults CornerTraveling with Mitochondrial Diseaseby Julie Martin


VacationTowarda Cure

Courtesy of

� Round trip air transportation fortwo to any American Airlinesdestination in the contiguous48 states, courtesy ofAmerican Airlines.

� $1,500 AAA gift voucher towardany cruise or vacation.

All proceeds to benefit the United Mitochondrial Disease Foundation.

Drawing Date: June 17, 2005.

Drawing will take place at theMitochondrial Medicine 2005Conference in St. Louis, MO.

$5 per ticket

$25 for book of 6 tickets

For more information on buyingor selling the tickets, please

contact UMDF at 412-793-8077.Contest rules are available on theUMDF web site and/or noted on

the raffle tickets.

Individuals who sell ten booksof tickets will win a UMDF

Throw (blanket)!

Official Airline of the United Mitochondrial Disease

Foundation

Attention Groups and Chapters:Sell Vacation Toward a Cure Tickets

and WIN!!!

$$$Cash$$$For all groups and/or chapters selling at

least $1,000 in raffle tickets.Your group sells together and then celebrates together

with a little extra cash for your next meeting!

You Could Win ...

Grand PrizeGroup or Chapter selling themost raffle tickets (at least

$5,000 in ticket sales)will WIN $1,000 in

scholarship money forsupport group/chaptermembers to attend the

2006 UMDF Symposium inAtlanta

YOU can helpTomato Face Foods

continue reaching thousandsacross the U.S. Do you

know someone in your local supermarket, schoolcafeteria, college food service, or grocery chain? If so,please contact Barbara and Allen at 216-382-0232 or

[email protected].

Allen, Barbara and Dana are still working on their goalto catch Oprah�s attention as well as other national

television production companies. Keep up the greatwork Tomato Face Foods!

Tomato Face Foods

Mitochondrial Disease Awareness Weekin Pennsylvania

The House of Representatives plans to designate the week of May 8-14, 2005 as "Mitochondrial Disease AwarenessWeek" and will urge all citizens of this Commonwealth to become better informed about the disease and its impact.

If you would like to spread the word through your local media in PA, please contact [email protected] for a press kit.


UMDF LEAP Award Living, Encouraging, Achieving & PersistingPurpose: To recognize an individual living positively with mitochondrial disease, highlighting the person'saccomplishments and volunteer service.

Eligibility: Age 14 years or older

Criteria: Individual with confirmed or suspected mitochondrial disease who overcomes daily challenges to achievegoals in career, family, and volunteer service. The individual demonstrates a positive attitude, hope for a brighter future,and an enthusiasm that inspires others.

UMDF Heartstrings AwardRecognizing a youth commitment that tugs on the heartstringsPurpose: To recognize a child or teen who has donated or raised funds for UMDF, enabling UMDF to continue itsmission.

Eligibility: The individual recognized must be under 18 years of age at the time of the donation or fundraising activity.

Criteria: The winner is chosen based on related criteria of age, time invested, talents demonstrated, effectiveness, andgenerosity. For nominees who implement fund raising projects, the judges will consider the uniqueness and creativity ofthe project, communication, the time invested, and the amount raised in comparison to the age of the individual. Fornominees who donate funds, the judges will consider the generous spirit shown, communication, and amount donated inrelation to the age of the individual.

Help UMDF Identify Everyday Heroes

Deadline for Nominations is April 1, 2005!!!! Nomination forms and more instructions are available on the UMDF Web Site at www.umdf.org.

Or request forms by calling Melinda at 412-793-8077 or emailing [email protected].

! February 12, 2005 - Pack the House Ice Hockeyfundraiser (Indiana Chapter)

! March 5, 2005 - 2nd Annual Bet on Baylee Casino Night(Ohio Chapter)

! March 5, 2005 - Writers at the Beach: Pure Sea Glass, aone-day writers� conference, in the Rehoboth/DeweyBeach area in Delaware. For more information, contactMary Beth Fischer at [email protected].

! April 16, 2005 - 2nd Annual �Mito-What?� 5K Run/Walkand Family Fun Day, Shrine of Our Lady of the Snows,Belleville, IL. For information, call Marsha Hohe at 618-233-6919.

! April 30, 2005 - Race for Riley, Whatever it Takes 5KWalk/Run and Tot Trot, Georgia Baptist Children�s Homein Palmetto, GA. (Atlanta Chapter)

! May 7, 2005 - 6th Annual Energy for Life Run/Walk(formerly Shelly�s Heroes) (DelVal Chapter)

! May 14, 2005 - 2nd Annual �Mito-What?� 5K Run and 1Mile Walk, Corporate Woods Founders Park (KC Chapter)

! May 20, 2005 - Hair cut-a-thon, Lake County Captainsbaseball game (Ohio Chapter)

! May 21, 2005 - Two events on one special day: aWalk in Chatham, NJ and a 5K Run/Walk in NorthHaven, CT (NY Metro Chapter)

! May 29, 2005 - Shadow Woodstock 2005, ChagrinFalls, OH (Ohio Chapter)

! June 4, 2005 - 3rd Annual Pittsburgh UMDF 5KRun/Walk at North Park

! June 4, 2005 - 4th Annual KFC/UMDF 5K Run/Walk,Forest Hills Park in Cleveland (Ohio Chapter)

! June 8, 2005 - 2nd Annual Ally Brunk Memorial 5KWalk/Run, Potterville, MI. For more information,email Daniel at [email protected].

! June 11, 2005 - Brew at the Zoo (DelVal Chapter)! June 15-18, 2005 - Mitochondrial Medicine 2005! July 18, 2005 - 6th Annual Ohio Golf Outing, The

Country Club, Pepper Pike, Ohio. For moreinformation, call Stan Davis at 216-581-0000.

! July 21, 2005 - 8th Annual Pgh UMDF Golf Outing,Churchill Country Club. For more information, callSandy at 412-793-8077.

! August 17, 2005 - 5th Annual Mito-What? Cruise inBay City, MI.

!! Mark your Calendars !!See pages 4-6 for more details on Chapter Events


ARIZONA#Arizona ChapterPresident: Suzanne PerrymanEmail: [email protected]

CALIFORNIA#Southern California ChapterPresident: Linda CooperEmail: [email protected]

FLORIDAContacts: Christine Golden

Carrie WatersEmail: [email protected]

GEORGIA#Atlanta Area ChapterContact: Holly CappEmail: [email protected]

INDIANA#Indiana ChapterPresident: Sue Ann BubeEmail: [email protected]

ILLINOISChicago Area GroupContacts: Gail Wehling Email: [email protected]

St. Louis Area GroupContact: Marsha HoheEmail: [email protected]

MARYLANDContact: Andrea Gropman, M.D.Email: [email protected]

MASSACHUSETTS#New England ChapterPresident: Bridget WillisEmail: [email protected]

MICHIGANContact: Ann ClarkPhone: 734-416-1115

Western MichiganContact: Suzanne MarousEmail: [email protected]

MISSOURI/KANSAS#Kansas City ChapterPresident: Pam JohnsonEmail: [email protected]

NEW YORK#New York Metro ChapterPresident: Mary PisaniEmail:[email protected]

New Paltz GroupContact: Beth and James DeArceEmail: [email protected]

OHIO#Ohio Chapter, Cleveland, OHPresident: Jennifer LymanEmail: [email protected]

Columbus GroupContact: Shawna SteeleEmail: [email protected]

Cincinnati GroupContact: Jennifer NealEmail: [email protected]

UMDF Chapters & GroupsOREGONContacts: Cathy Akins and Cori FeistEmails: [email protected]

[email protected]

PENNSYLVANIA#Delaware Valley ChapterPresident: Maripat ShellyEmail: [email protected]

Pittsburgh GroupContact: Karen WilsonEmail: [email protected]

SOUTH CAROLINAContact: Karis MottEmail: [email protected]

TEXASContact: Tova SidoEmail: [email protected]

VIRGINIAContact: Shelby HawthorneEmail: [email protected]

WISCONSINEmail: [email protected]

OUTSIDE OF THE UNITED STATES

AUSTRALIAContact: Tara CollyerEmail: [email protected]

New groups forming in Rhode Island andDenver. Interested in starting a group inyour area? Contact [email protected].

Attention all UMDF Members!!UMDF Database Under Construction

Dues Renewal Notices:We ask for your patience during our transition period in upgrading theUMDF computer system and web site. If you have received a dues

renewal notice and have already paid your dues, please [email protected] or call Alisia at 412-793-8077. This will help our

computer consultants alleviate such issues in the future.In addition, we are currently unable to process networking requests.We hope to have a new and improved system operating during this

quarter. Your patience is appreciated.

NONPROFIT ORG.U.S. POSTAGE

PAIDPittsburgh, PA

Permit No. 4899

Volume 10 � Issue 1 � Winter 2005

In This Issue:Worms with Mitochondrial Diseases . . . 1Ask the Mito Doc. . . . . . . . . . . . . . . . . . 2Chairman�s Report . . . . . . . . . . . . . . . . 3Chapter Activities . . . . . . . . . . . . . . . . 4-6Development Corner. . . . . . . . . . . . . . . 7Mitochondrial Medicine 2005 . . . . . . . . . 8Fundraisers. . . . . . . . . . . . . . . . . . . . . . 11Mito Adults Corner . . . . . . . . . . . . . . . . 16Vacation Toward a Cure. . . . . . . . . . . . 17LEAP and Heartstrings Awards . . . . . . 18

Deadline for next issue is 4/1/05

UMDF MISSIONTo promote research and education for the diagnosis, treatment

and cure of mitochondrial disorders and to provide support toaffected individuals and families.

8085 Saltsburg Road, Suite 201Pittsburgh, PA 15239Phone 412-793-8077

Fax 412-793-6477email: [email protected]://www.umdf.org

© The United Mitochondrial Disease Foundation.All rights reserved.

UMDF�s intent is to keep you informed - we askthat you always discuss any diagnoses,

treatments, or medications with your personalphysician. UMDF assumes no liability for any

information in the Mitochondrial News.

If you have an event announcement or anidea for an article for the Mitochondrial News,

please email [email protected]. We want tohear from YOU!

For information on starting a fundraiser inyour area, email [email protected].

The UMDF Office StaffWe�re Here to Help You! 412-793-8077

Chief Financial OfficerMark Campbell, [email protected], ext. 101

Member ServicesJean Bassett, [email protected], ext. 105

Donna Nameth, [email protected], ext. 109Lindsay Houston, [email protected], 107

Melinda O�Toole, [email protected], ext. 103Alisia Verenna, [email protected], ext. 104

Communications/NewsletterKara Strittmatter, [email protected], ext. 106

Fundraising/Special EventsSandy Turi, [email protected], ext. 102

DevelopmentJulie Martin, [email protected], ext. 113

United Way & Matching GiftsToni Beasley, [email protected], ext. 114

umdf winter 2005 final · worms with mitochondrial diseases bernard lemire, ph.d. department of...

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