Transcript No Slide Title

Peptide Hormones
Evolving Considerations for
Biotechnology and Clinical Medicine
Mainstream vs. Fad
Chanda Zaveri, M.S.
Founder & Chairman
Activor Corporation
Peptide Hormones
Features & Definition
Modify protein structure and state of
activity
Are not metabolized by virtue of their
activity
Hormone receptors – allosteric
proteins
Peptide hormones – allosteric effectors
Peptide Hormone Physiology
• Act on cell membrane
• Act via secondary mediators
• cAMP
• Diacylglycerol
• Calicum
• Tyrosine kinase
Bioengineered
Peptide Hormones
• Modification of existing protein
• Consider primary, secondary or tertiary
structure as targets
• Change in structure – new physiologic
effect
• Creation of novel protein
Secretagogues as Biotech Targets
• Control peptide hormone synthesis
and secretion
• Three classes reported classically
• Releasing factor hormones – GHRF
• Central effectors
• Hypoglycemia, dopamine, deep sleep, amino
acids
• Other peptide and steroid hormones
• Cortisol, estrogen, thyroid hormone
HTA-5: Novel Peptide Hormone
• Primary structure derived from thymic
hormone, with bioengineered
modifications
• Physiological effect is dose dependent
and cumulative
• GHRF – low dose
• Immunomodulation – high dose
TF-5 Literature Review
•  mitogenic T-cell response (Thurman, 1975)
• Modulates incidence of GVHD (Fast, 1990)
• Enhances NK activity of normal LGL (Serrate 1987) and tumor
bearing mice (Mastino, 1992)
• Increases tumor specific immunity
•  cytotoxic T-lymphocyte response (Zatz & Goldstein, 1983)
•  antigen-presenting capacity of macrophages (Tzehoval,
1989)
• Stimulates proliferation of, and IL-6 production in, rat
splenocytes (Attia & Badamchian 1993)
Growth Hormone vs. Age
J. NIH Research
April 1995
FDA Treatment Guidelines - hGH
• Hypo-Pituitarism
• Adult-onset Growth Hormone
Deficiency
hGH Supplementation
Why are people using this?
• Looking for “anti-aging” effect
• Subjective Reports
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Improved memory
Enhanced sexual performance
Mood elevation
More restful sleep
Enhanced exercise performance
Decrease in incidence of hot flashes
Theories of Aging
• Oxidative Stress Theory
• Genetic Theory of Aging
• Theory of Somatopause
• Hormonal Theory of Aging
• Links aging to a decline in the body’s
secretion of hormones WITHOUT any loss
in its ability to respond to these hormones
hGH Supplementation (OFF LABEL)
• Objective Reports
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 bone density
 immune function
 rate of wound healing
 HDL,  LDL
 in LBM,  LPL
 blood pressure
 cardiac output
 skin thickness and hair growth
General Insulin-like effect
Primary hGH Mechanism
HTA-5 Pilot Study Profile
• 15 Subjects
• 7 Male & 8 Female
• Age Range: 32 - 70 years
• Test Duration: 6 weeks
• Preparation: HTA-5 + Lysine + Arginine
• Dosing: 1x daily
• HTA-5: 20ng; Lys: 1200mg; Arg: 1200mg
• Exclusion Criteria: [IGF-1]400ng/mL
Subjective Reports
(combined study)
• Improved sleep patterns
• Enhanced exercise stamina
• Improvement in skin texture and thickness
• Decreased rate of hair loss
IGF-1 Physiology & Endpoint
Considerations
• Glucose Metabolism
• Exerts insulin-like effect
• Increases glycogen storage in SKM
• Inhibits basal & insulin stimulated lipogenesis via LPL
• Cholesterol Metabolism
• ? Increase in hepatic cholesterol receptors
• ? Suppressed synthesis
• Osteoblast Metabolism
• Binds to osteoblast receptor – stimulates new bone
formation
• IGF-2 > IGF-1
IGF-1 Response
MEN
WOMEN
HTA-5
HTA-5 + AA
Male/Female IGF-1 Response
• HTA-5 stimulates IGF-1 response
• Avg  IGF-1: 40.4%; > 50 years: 56.8%
• Co-administration with known RFs - Synergistic
IGF-1 response
• DEDUCED: HTA-5 is GHRF
• Generalizations
• Female IGF-1 response is double that of males
• IGF-1 response is age dependent
• Endpoint data suggests a heightened female
response
Total Cholesterol (mg/dL)
30-45
46-59
60+
Total Cholesterol (mg/dL)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Cholesterol
Initial
Final
231
181
270
189
257
241
240
237
241
231
253
223
219
209
259
233
239
217
241
225
214
203
237
215
218
211
247
222
251
239
Difference
0
-50
-81
-16
-3
-10
-30
-10
-26
-22
-16
-11
-22
-7
-25
-12
-2
Average % Decrease
Subject
-4
-6
-8
-10
-12
-14
-16
30-45
46-59
Age Group
60+
M ale
Female
Male/Female Cholesterol Response
• Avg  Total Cholesterol: 23 mg/dL
• Decrease in serum cholesterol
• No dietary modifications
• No change in medical regimen, if any
• No lifestyle modifications
Bone Density (g/cm2)
• Radial ultrasound
16
• Average Increase
• 6.8% HTA-5
• 12.6% HTA-5 + AA
MALE
FEMALE
14
12
10
8
M
6
F
4
2
0
30-45
46-59
60+
MEN
WOMEN
ATM LBM
10
10
Average % Change
Average % Change
Body Composition (kg)
5
0
-5
-10
-15
-20
5
0
-5
-10
-15
-20
30-45
46-59
Age Group
60+
30-45
46-59
Age Group
60+
Body Composition Response
• Objective changes in TBC
•Avg %  ATM: 14.8%
•Avg %  LBM: 4.1%
•Slight  across age groups
•Avg %  body weight: 13.2%
•No dietary or lifestyle modifications
Case Reports
Reversion of immuno-suppression
Cure of chronic active hepatitis B
infection
Biotech Industry
Considerations
Conclusion