Treating Mitochondrial Disease/Dysfunction in Autism

In my book I will be covering the science behind hopefully almost all autism, which then naturally leads to translating it into therapy.  In the ideal world you would just skip straight to the therapy and the final section of the book will be just that.  Clearly it would make sense to read the science first, so that you know what are the dysfunctions that you might need to treat.

Hopefully there will also be some case studies from people who have applied a science-based approach to identify and implement effective therapies.

Roger would clearly make a very good example of a reversible in-born metabolic-caused type of autism.

I will be posting on my blog some drafts from the Part III - Translating Science to Treat Autism.  This is of course just one person's collection of other people's ideas and some of his one.  The reader and his/her medical medical team ultimately decide what to implement and must monitor its ongoing implementation.

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Mitochondrial disease is managed rather than cured. It seems to be present in autism in widely varying degrees of severity.  Extreme cases result in very severe regressive autism with MR/ID.

It is either diagnosed based on detailed analysis of numerous blood tests, or more recently via a sample taken from inside the cheek. These tests cannot be perfect, because mitochondrial disease can be organ-specific.

Someone with body-wide mitochondrial disease will have poor exercise endurance and this will be very noticeable compared to siblings and peers.

Dr Kelley, from Johns Hopkins, has published his therapy for autism secondary to mitochondrial disease (AMD):-

1.      Augment residual mitochondrial enzyme complex I activity

2.      Enhance natural systems for protection of mitochondria from reactive oxygen species

3.      Avoid conditions known to impair mitochondrial function or increase energy demands, such  as prolonged fasting, inflammation, and the use of drugs that inhibit complex I.

Combining the first and second parts of the treatment plan, the following is a typical prescription for treating AMD:

L-Carnitine 50 mg/kg/d                Alpha Lipoic acid 10 mg/kg/d

Coenzyme Q10 10 mg/kg/d          Pantothenate 10 mg/kg/d

Vitamin C 30 mg/kg/d                  Nicotinamide 7.5 mg/kg/d (optional)

Vitamin E 25 IU/kg/d                   Thiamine 15 mg/kg/d (optional)

There are actually five stages in the OXPHOS process in mitochondria and there are five enzyme complexes. Dr Kelley's plan above is for the most common dysfunction, complex 1.

Different clinicians have different treatments.

Also appearing elsewhere are :-

Calcium folinate (2 x 25 mg), but not because of peroxynitrite

Biotin 5-10 mg/day

NAC

Methylcobalamin B12

Creatine

On the basis that peroxynitrite, from nitrosative stress, damages the mitochondria, you might consider:

·         Calcium folinate (leucoverin) in very high doses like 25mg twice a day.

·         Xanthine oxidase inhibitors, typically used to lower uric acid to treat gout. A good example is Allopurinol. It will both lower uric acid and peroxynitrite. Uric acid is itself a potent scavenger of peroxynitrite; this may look odd given the previous sentence. If someone has low uric acid and wants to reduce peroxynitrite then uric acid itself should be therapeutic. The purine metabolism may play a key role in some types of autism, as proposed by Professor Robert Naviaux.

·         Rosmarinic acid, a natural scavenger of peroxynitrite.

There are many anomalies in autism and one is uric acid.  Some people have low levels and some have high levels. Uric acid is itself a scavenger of peroxynitrite.  People with high levels of uric acid do get gout, but almost never MS (multiple sclerosis) and it has been suggested that scavenging peroxynitrite is neuroprotective.

Special, electrically charged, antioxidants have been developed to target the mitochondria.  MitoE is a charged version of vitamin E and MitoQ is a charged version of coenzyme Q10.

Based on the research, you might  also seek to activate PGC-1α, the master regulator of mitochondrial biogenesis. This can potentially be achieved via:-

·         Exercise  (gradual endurance training)

·         Activate PPARγ and perhaps  PPARα (e.g. Bezafibrate  and Rosiglitazone)

·         Activate AMPK (Metformin)

·         Activate Sirt-1 (resveratrol and other polyphenolic ‎compounds)

Carnitine-like analogs may also help in theory.  The standard L-Carnitine, widely used as a supplement, is very poorly absorbed even at high doses. An analog is a modified version of a molecule that keeps the therapeutic beneficial effect, but overcomes a drawback, bioavailability in the case of carnitine. There is some basis in the literature to believe that the Latvian drug Mildronate might be useful to treat complex 1 mitochondrial dysfunction.



more detail at  https://epiphanyasd.blogspot.com/2017/02/mitochondrial-disease-and-autsim.html