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RCDP
Program Highlights
PROGRAM
STATUS
Issue 2, April 2016
Drug tested in
animals

Drug discovered

Pre-trial
measurements
Observational
trial

Interventional
trial
The current focus is on finalizing the observational trial design and further analysis of the pre-trial blood sample results.
Pre-trial Measurements Results
We completed our preliminary study of the serum collected from the six amazing volunteer families, and we are very excited to share some of
the results with all of you.
We compared the average metabolite levels detected in the unaffected siblings (n=7) and each of the RCDP kids. The results in the table below
are presented as a percent of the siblings’ levels (the average sibling level is treated as 100%). For example, if the value in the table is 75, that
means the child had 75% of the level the unaffected siblings had; in other words they had 25% less of that metabolite. The results are also
illustrated in the graphs following the table, with explanations of the results.
Both the DHA and oleic acid containing ethanolamine plasmalogens (PlsEtn) are low in RCDP (with most levels less than 50% of the siblings).
Three RCDP children have plasmalogen levels between 30-67% of what was detected in the unaffected siblings, and four RCDP kids have levels
that are under 25%.
Relative Plasmalogen Levels
Most plasmalogens are a major class of ethanolamine phospholipids. The other major class of ethanolamine phospholipids is the
120.0
phosphatidylethanolamines
(Ptd). So, in addition to looking at the absolute plasmalogen levels (PlsEtn), it is also informative to look at the
plasmalogen phosphoethanolamine level relative to the non-plasmalogen phosphoethanolamines (Pls/Ptd). This relative level may be more
indicative of the availability of the plasmalogens. Can you guess which famous RCDP child is RCDP1 based upon the relative levels?
Relat
to un
>
Absolute PlsEtn Levels
80.0
20.0
Relative levels compared
to un-affected siblings
100.0
60.0
40.0
Relative to Respective PtdEtn levels
120.0
Percent of sibling levels (%)
Percent of sibling levels (%)
100.0
> 75%
B
80.0
60.0
25-75%
40.0
<
20.0
0.0
DHA (22:6)
0.0
Oleic acid (18:1)
1 2 3 4 5 6 7
1 2 3 4 5 6 7
DHA (22:6)
PlsEtn
Oleic acid (18:1)
DHA (22:6)
1 2 3 4 5 6 7
DHA (22:6)
PlsEtn
Un-affected
Siblings1
RCDP
Un-affected Siblings
RCDP 33
RCDP
RCDP
4
RCDP
4 5
RCDP
RCDP 6 5
RCDP
Oleic acid (18:1)
Oleic acid (18:1)
Pls/Ptd
RCDP
1
RCDP
2 2
RCDP
< 25%
1 2 3 4 5 6 7
Pls/Ptd
RCDPRCDP
7
6
RCDP 7
1 of 2
www.phenomenome.com
1-306-244-8233
Saskatoon, Saskatchewan, Canada
RCDP Program Highlights
Peroxisomal β-oxidation 22:6/22.4
Percent of sibling levels (%)
cytoplasm/endoplasmic reticulum
Relative levels compared
to un-affected siblings
Relative levels compared
to un-affected siblings
300.0
250.0
200.0
fatty acid elongation
normal
>75%
> 75%
phospholipid biosynthesis
150.0
peroxisome
100.0
peroxisomal β-oxidation
normal
25-75% 25-75%
Between
50.0
<25%
< 25%
0.0
plasmalogen synthesis
lowered
fatty alcohol synthesis
normal
Peroxisomal β-Oxidation
Peroxisomal β-oxidation is a metabolic process that makes acetylCoA, which is used to make the fatty alcohol that becomes part of the
plasmalogen molecule. We can check to make sure this system is
working by looking at the ratio of product metabolites to precursor
metabolites. None of the RDCP children had impaired peroxisomal βFatty Alcohol C16:0
oxidation.
Relative levels compared
Percent of sibling levels (%)
120.0
Relative
levels compared
to un-affected
siblings
to un-affected siblings
100.0
Meet Dushmanthi
>75%
> 75%
80.0
60.0
25-75% 25-75%
Between
40.0
20.0
<25%
< 25%
0.0
Fatty Alcohol Levels
The metabolic system impaired in RCDP involves the attachment of
the peroxisomally synthesized fatty alcohol to the glycerol backbone
to make the ether glycerol bond unique to plasmalogens. Therefore,
we checked to see if these fatty alcohols were accumulating in the
RCDP children. However, fatty alcohol levels were found to be
normal, indicating that the metabolites are being utilized in another
biochemical pathway, so
GTAno
446increase is observed.
Relative levels compared
Relative
levels compared
to un-affected
siblings
to un-affected siblings
120.0
Percent of sibling levels (%)
Observational Trial
The anticipated start date of the observational trial is Summer 2016!
All families will have the opportunity to participate in this trial. More
information is coming soon.
100.0
> 75%
>75%
80.0
60.0
25-75%25-75%
Between
40.0
20.0
< 25%
<25%
0.0
GTA Levels
In addition to the critical role that plasmalogens play in membrane
functions, they are also the body’s principal free radical scavenger
and are potent anti-inflammatory agents. GTAs are potent antiinflammatory very long chain fatty acids. All but one RCDP child have
reduced levels of these lipids in comparison to the siblings. These
results warrant further investigation. Either there is a reduced ability
to make these metabolites or they are being consumed as
compensation for lower plasmalogen levels.
www.phenomenome.com
Dushmanthi, a Metabolic Research
Specialist, has been at PDI for ten
years. She developed the
acylcarnitine and free fatty alcohol
methods to analyze blood samples
for the RCDP trial to assess how the
disease has affected the regular
cell functions of a person.
Phenomenome is Restructuring
Phenomenome Discoveries Inc. (PDI) was founded in 2000. Since its
founding, PDI has developed a diverse array of novel diagnostic and
therapeutic technologies encompassing 20 patent families and has
built extensive supporting infrastructure for these assets. PDI’s
facilities are FDA-compliant for drug manufacturing and ISO
13485:2003 certified to manufacture in vitro diagnostic devices
(IVDD); in addition, PDI operates a licensed medical laboratory that
is certified by the College of American Pathologists (CAP) and CLIA.
Irreconcilable differences arose among the shareholders of PDI
regarding the future direction of PDI. Attempts to resolve these
issues by the PDI Board of Directors were unsuccessful. Under the
circumstances, the parties consented to the funding and
appointment of an independent court-appointed receiver (FTI
Consulting Inc.) to organize the asset portfolios of PDI such that the
therapeutics, diagnostics, and laboratory businesses of PDI can
obtain independent funding for their continued development. PDI
will continue operations during this process, which is expected to
take several months to complete. I am working closely with the
receiver to ensure that this transition will have minimal disruption
to its ongoing research and clinical trial programs.
I’m looking forward to seeing all of you at the Rhizo Kids conference
in July.
Sincerely,
Dr. Dayan Goodenowe
1-306-244-8233
2 of 2
Saskatoon, Saskatchewan, Canada