Top 10 Takeaways

from

the UMDF 2014

Mitochondrial Disease Symposium

in Pittsburgh PA, June 6-8, 2014

1. Scientific Meeting- Leonid Sazanov presented specifically on the structure of complex 1. He commented also on how the well-known cplx 1 inhibitor ROTENONE (pesticide) works. I was a bit surprised to learn that the structure of complex 1 was only recently elucidated. For those who are new to the term: Complex 1, watch this short video for a primer in how complexes 1-5 make energy (ATP) in our mitochondria.

Tweet- #Mito2014 Leonid Sazanov speaking about the importance of Complex 1 in#LHON, #parkinsons and #cancer. All 44 subunits of it!!

2. Scientific Meeting – Matthew Hirschey (twitter- @hirscheylab) spoke about Protein modification and mito. He discussed acetylation and hyperacetylation and introduced newer modifications- malonylation, succinylation and glutarylation. He also introduced (at least is was new to me!!) a class of proteins calls SIRTUINS. The Deacylases (SIRT 3,4,5) have new-found impact on mitochondrial dysfunction.

tweet: #mito2014 Hirschey from Duke gene may be fine, protein may be fine but the group you are putting on the protein may be wrong… i.e.. Acetylation. Then talked about sirtuin and how it regulates de-acetylation

3. Mitochondrial Disease and Dysfunction is linked to MANY other fields of medicine specifically CANCER and CARDIOLOGY. Michael Lotze gave a talk about mitochondria and cancer cells dying a wrongful death (mentioning HMGB1 in innate and adaptive immunity) and Stephen Archer gave an overview of new therapeutic targets for Cancer and Cardiovascular Disease (focusing on the DRP1 protein that mediates fission).

4. Scientific Meeting- Parkinson’s disease is a disease process that involves the mitochondria. In mouse models, giving the mice chronic doses of ROTENONE induces Parkinson’s like symptoms. ROTENONE is a potent complex 1 inhibitor, it is also an ORGANIC pesticide (NOT a rat poison as was conveyed in the family session) that has recently been limited in the United States. (good overview or Rotenone use here)

This piece of information BEGS to question… what is Rotenone and other pesticides impact on individuals with Complex 1 (and other mitochondrial deficiencies)?? I urge the UMDF and the mitochondrial scientific community to have this question at the top of their agenda at NEXT YEAR’s meeting~ WHAT ENVIRONMENTAL EXPOSURES MAKE MITOCHONDRIAL DISEASE SYMPTOMS BETTER or WORSE for Patients?

(some other research papers I came across regarding rotenone/mitochondrial/parkinson’s link-

http://www.ncbi.nlm.nih.gov/pubmed/19042691

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1175899/

http://www.sciencedirect.com/science/article/pii/S0969996109001685

Tweets:

#mito2014 environmental links to Parkinsons- Rotenone (acute and chronic) MPTP all been found to impact mitochondrial function.

#mito2014 focused on an #environmetal #toxin model- chronic rotenone exposure in cell culture

#mito2014 If you grow HeLa cells in galactose and glutamine they become dependant on their mitochondria for energy vs. glucose medium.

autism panel 5. Family Meeting-Mitochondrial disease and Autism are intimately intertwined. Dr. Bob Naviaux shared his research about purine signaling and cell danger response and how antipurinergic therapy (suramin) increases mitochondrial function in a mouse model of autism (reference here), Dr. Richard Frye shared his research about oxidative stress induced mitochondrial dysfunction in a subset of cell lines from autistic children (a more thorough discussion of this research can be found here), and Dr. Doug Wallace talked about changes in mitochondrial DNA heteroplasmy and its impact on inflammation as well as halogroups and which ones may be more at risk for autism. You can listen to the talk replay of this panel here.

Questions from this session inquired about what types of “environmental toxins” would be important to avoid for a child with mito and autism. Dr. Bob Naviaux was kind enough to provide this slide (and give his permission for sharing) that highlights 12 tips that families can focus on:

Slide thanks to Dr. Naviaux

#mito2014 Haplogroups J, N, V, T, T2 all increased risk. some have almost as big effect as sex bias (boys vs. girls)

#mito2014 subtle changes in heteroplasmy in mitochondrial mutant can cause phase change in symptoms – such as in response to inflammation and regression

6. Family Meeting- Dr. Bruce Cohen of Akron’s Children’s Hospital gave this presentation on Dysautonomia and Mitochondrial disease. The biggest take away I had was that dysautonomia is definitely linked to mito but no one really knows if it is just another symptom or a cause unto itself- chicken or the egg!? Cohen spent much of the talk focusing on primary, secondary and possible mitochondrial disease, with the bulk of his patient population (including cases he has recently re-classified from mitochondrial disease to possible mito), over 80% being possible mitochondrial disease.

tweets:

#mito2014 Cohen estimates (in his patient population) 15% primary mitochondrial disease (genetic confirmation) 1% secondary and the rest (over 80%) are “possible” mitochondrial disease

#mito2014 Cohen explains reclassification of patient who in 1992 was complex 1 with MELAS like mitochondrial disease, to 2013 she is reclassified as possible mitochondrial disease, she doesn’t fit criteria, though he believes in his heart she has it. Takeaway- classification for primary mito has changed over last 20 years.

7. Muscle Biopsy is NOT the gold standard anymore. Even with a positive muscle biopsy for mitochondrial disease, a primary mito diagnosis will not necessarily be given. Both Cohen and Parikh noted this in their talks. Dr. Sumit Parikh’s overview of Mito talk from this year’s symposium can be watched here.

8.Family Meeting- Dr. McCormack, CHOP endocrinologist This doctor gave quite a few pearls of wisdom about how the mitochondrial system and the endocrine system interact (talk can be viewed here).

#mito2014 high levels of steroids over a long period of time are TOXIC to#mitochondria look at- steroid myopathy in ICU patients

#mito2014 Symptoms of adrenal insufficiency low blood sugar, low blood pressure, low sodium levels esp with illness. FIRST STEP of hormone production is IN the mitochondria

#mito2014 high levels of steroids over a long period of time are TOXIC to#mitochondria look at- steroid myopathy in ICU patients

#mito2014 a lot of seizure meds disrupt vitamin D metabolism

#mito2014 Parathyroid dysfunction if calcium level are abnormal – consider 25-OHD level (vitamin D levels) optimal should be ABOVE 30 but higher is better..

9. Family Meeting- Clinical trials update- the leader in the race to a treatment for mito is still EPI-743 and an overview was given of the current clinical trials and hopefully FDA approval in the coming years. A few other smaller trials are popping up but they are narrow in focus (MELAS, etc). If the clinical update video is made available I will post it here.

10.Family Meeting- Medical Child Abuse and Munchausen By Proxy allegations and the impact of the Justinia Pellitier case has sent an earthquake (and many lingering shock waves) through the mitochondrial community. Dr. Korson (Justina’s doctor who diagnosed her with mitochondrial disease) gave this very informative talk about “Navigating the Challenges and Risks in Patient Care (in a world still learning about mitochondrial disease)” which the replay can be found here.

Plus +1

11. Dr. Korson presented a great talk on significance of specific lab values in mitochondrial disease. So many pearls of wisdom in this talk. (this talk is available for replay here).

Dr. Vockley kicked off the scientific session on the first day (along with co-organizer Dr. Amy Goldstein) by saying this…. and I find it a good summary of the conference as well:

#mito2014 Vockley- single gene changes don’t sufficiently describe/account for the phenotype for mitochondrial disease… And mitochondria are complicated!!

I would whole-heartedly agree!! And add… we need to move BEYOND just SINGLE GENES and look much more closely at our ENVIRONMENT and GENE-ENVIRONMENT Interactions!

Editor’s Note- My personal highlight of the symposium was being able to see old friends and meet new ones! Getting to see this dear friend who came all the way from Texas to visit, topped my list! Miss her and her sweet boy! Her blog about the conference can be found here.

Editor’s Note- Here are a few more links that have been added by the UMDF to the video archives:

Scientific Summary Panel

Ask the Mito Doc – Adult

Ask the Mito Doc- Child

SSI disability and transition from child to adult