Re: Quest Magazine Article...

[Guest guest]

It is hard to find the words to thank you all for being there and providing support and encouragement whenever it has been needed most.

I pray the holidays bring good cheer to all the families affected by these illnesses and that God especially bless our children - to be pain free, vigorous and filled with joy.

I pray God's healing touch reach them all in the coming year.

God bless you all, too.

Merry Christmas! Happy New Year!

Virginia, Emma's Mom (16 months, Complex I)

P.S. Congratulations on the Quest article and on Jay and family being reunited for holidays. So great to hear the news.

Virginia M. Buchanan

[Guest guest]

Terri,

I read the article and my chest was filled with pride and I am very

proud to know Carl. The article is great and a tribute to a great

Mom.

Happy Holidays! Give Carl a big hug from me.

Alice

[Guest guest]

Terri, Carl is just precious. I enjoyed the article. Thanks for sharing your little guy with all of us. I hope all the testing in 2001 shows good things for him and the improvement you anticipate.

God bless him this Christmas and always!

Virginia, Emma's Mom (16 months, Complex I)

Virginia M. Buchanan

[Guest guest]

Dear Terri:

Great article and what a handsome boy you have! He looks like he really likes the computer and must have fun learning with it.

I am glad that he is doing ok.....am thinking of both of you a lot.....

Love, Trish

Quest Magazine Article...

I'm showing off my handsome guy again... MDA recently did an article on vision problems associated with neuromuscular disorders and included a little piece on my son Carl. The article can be read at http://www.mdausa.org/publications/Quest/q76eyecare.html and if you go down a ways you'll see the heading "A child copes with low vision and mitochondrial disease" - that's my boy! If you receive the Quest magazine in the mail he's on page 15.

They also covered ptosis which I know a lot of people on this list are dealing with so you might want to check the rest of the article out as well.

Terri

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[Guest guest]

I just wanted to thank you all for your wonderful comments about Carl and the article in Quest - and wish you all Happy Holidays! I hope the new year brings improvements for everybody and a speedy start to the Uridine trials!

TerriGet your FREE download of MSN Explorer at http://explorer.msn.com

[Guest guest]

what is uridine for? where are trials starting? thanks!

virginia, emma's mom - holding her now

Virginia M. Buchanan

[Guest guest]

Well I was hoping that somebody smarter than I am would answer this, but

I'll give it a shot. Please don't take this as absolute fact either because

I'm just trying to put everything I've read/heard into plain English and

could very well be screwing the whole thing up! (Steve - feel free to jump

in and save me anytime...)

Uridine is something either used in, or created by, pyrimidine metabolism

(I'm not sure which one) - which apparently relies on normal functioning

mitochondria to work effectively and mitochondria are supposedly dependent

on uridine. Therefore it's hypothesized that people with mitochondrial

disorders could be deficient in Uridine which again could be contributing to

the symptoms/progression of the mitochondrial disorder.

Initial studies with uridine were kind of hard because it is not absorbed

very well - only something like 5% - and you had to give a LOT of it to get

therapeutic levels. Then there was a " pro-drug " (I'm not sure what that

means) created that was called triacetyluridine, or PN401 - which was 5-10

times more efficient.

The following abstract was from early 1999 and presented at the SIMD

conference in March. This information deals specifically with improvement

of Renal Tubular Acidosis (RTA). I had something a while back that talked

about improvements in language, ataxia, seizures and other neurological

problems with uridine treatment but I can't seem to find it now - I'll keep

looking.

The trials will likely start in San Diego and have other sites that will be

part of the trials. Based on press release that we recently saw on the

list, I'm unsure if they will be using " normal " uridine or if the drug

company involved either has, or will be developing for the trials, a better

absorbed " version " .

I hope this helps. This is something that has been going on for years and

I'm thrilled to see they have found a drug company and that the trials might

actually get moving!

Terri

====================================

Abstract Submitted for Presentation

Society for Inherited Metabolic Disorders Annual Meeting

Correction of Renal Tubular Acidosis (RTA) in Mitochondrial Disease

Patients Treated with Triacetyluridine (PN401).

R.K.Naviaux, K. McGowan, B.A.Barshop, W.L.Nyhan, R.H.Haas. The

Mitochondrial and Metabolic Disease Center (MMDC), University of

Californa School of Medicine, 200 West Arbor Drive, San Diego, CA

92103-8467.

Background.

Patients with a variety of different mitochondrial disorders may be

functionally deficient in uridine. De novo pyrimidine biosynthesis is

dependent on normal mitochondrial function and is coupled to the

mitochondrial respiratory chain via ubiquinone and the enzyme dihydroorotate

CoQ oxidoreductase (DHO-QO, EC 1.3.99.11), also known as dihydroorotate

dehydrogenase (DHOD, EC 1.3.3.1). Cells with mitochondrial dysfunction in

culture are known to be completely dependent on exogenous uridine for growth

and survival because of a functional deficiency in the activity of DHO-QO.

Triacetyluridine (PN401) is a prodrug of uridine that is rapidly converted

to uridine by non-specific esterases in the gastrointestinal epithelium

after oral delivery. PN401 exhibits 5-10 times the bioavailability of

unmodified uridine, permitting the achievement of therapeutic blood levels

of uridine with substantially less drug.

Patients.

Four patients with mitochondrial RTAs were studied. Mitochondrial RTAs often

defy simple classification as proximal (type II) or distal (type I)

tubulopathies, as these patients are often mosaics and express features of

both phenotypes leading to hyperchloremic (non-anion gap) metabolic

acidoses. Patient #1 was a 2 year old female with Leigh syndrome, lactic

acidemia, and complex I deficiency who required 200 mEq/day of NaHCO3 to

compensate for renal losses of alkali, and maintain serum bicarbonate levels

above 20 mEq/l, 1+ proteinuria, and significant aminoaciduria with

hydroxyprolinuria. Patient #2 was a 3 year old female with Leigh syndrome,

and complex IV (COX) deficiency, who also required 200 mEq/d of NaHCO3.

Patient #3 was a 2 year old male with Leigh syndrome, lactic acidemia, 1+

proteinuria, and pyruvate dehydrogenase (PDH) deficiency, who required up to

210 mEq/d. Patient #4 was an 11 year old male with 3-hydroxyisobutyric

aciduria, lactic acidemia, and encephalomyopathy, who required 468 mEq/day.

Methods.

Blood and urine electrolytes, creatinine, pH, urinalysis, and venous blood

gases were studied before and after treatment. Quantitative urine amino

acids and organic acids were also obtained. Pre-enrollment doses of oral

sodium bicarbonate were continued for the first 3 days of PN401 treatment,

then reduced weekly as tolerated to maintain serum bicarbonate above 20

mEq/l. Treatment. Patients received triacetyluridine (PN401) 2 g/m2 PO TID.

Results. Patient #1 experienced complete correction of her RTA within 24

hours of treatment, maintaining a serum bicarbonate of more than 20 mEq/l

without any further oral bicarbonate. She also had complete resolution of

her hydroxyprolinuria within 2 weeks. Urinary bicarbonate losses in patient

#2 were initially 99 mEq/l. The fractional excretion of bicarbonate

(FEHCO3) was 9.3% prior to therapy. After 36 hours on treatment with PN401,

urinary bicarbonate losses were undetectable (<5 mEq/l). After 3 weeks of

treatment, just 25% of the patient’s pre-enrollment dose of bicarbonate was

needed to maintain normal serum bicarbonate. Urinary bicarbonate losses in

patient #3 were 59 mEq/l. The FEHCO3 was 10.0% prior to therapy. After 36

hours of treatment wth PN401, urinary bicarbonate losses were undetectable

(<5 mEq/l). After 3 weeks of treatment the patient required just 10% of his

previous dose of bicarbonate. Patient #4 has been treated for 1 week and

has had a 35% reduction in his oral bicarbonate requirement.

Conclusion.

Renal tubular acidosis was corrected or dramatically improved in 4 out

of 4 patients with mitochondrial disease treated with triacetyluridine

(PN401).

======================

>From: Ginny581@...

>Reply-To: Mitoegroups

>To: Mitoegroups

>Subject: Re: re: Quest Magazine Article...

>Date: Mon, 25 Dec 2000 18:48:51 EST

>

>what is uridine for? where are trials starting? thanks!

>

>virginia, emma's mom - holding her now

>

>Virginia M. Buchanan

_________________________________________________________________

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