Peptide Hormones

1
Peptide Hormones

• Evolving Considerations for Biotechnology and
  Clinical Medicine
• Mainstream vs. Fad
• Chanda Zaveri, M.S.
• Founder Chairman
• Activor Corporation

2
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

3
Peptide Hormone Physiology

• Act on cell membrane
• Act via secondary mediators
• cAMP
• Diacylglycerol
• Calicum
• Tyrosine kinase

4
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

5
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

6
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

7
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)

8
Growth Hormone vs. Age
J. NIH Research April 1995
9
FDA Treatment Guidelines - hGH

• Hypo-Pituitarism
• Adult-onset Growth Hormone Deficiency

10
hGH SupplementationWhy are people using this?

• Looking for anti-aging effect
• Subjective Reports
• Improved memory
• Enhanced sexual performance
• Mood elevation
• More restful sleep
• Enhanced exercise performance
• Decrease in incidence of hot flashes

11
Theories of Aging

• Oxidative Stress Theory
• Genetic Theory of Aging
• Theory of Somatopause
• Hormonal Theory of Aging
• Links aging to a decline in the bodys secretion
  of hormones WITHOUT any loss in its ability to
  respond to these hormones

12
hGH Supplementation (OFF LABEL)

• Objective Reports
• ? 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

13
Primary hGH Mechanism
14
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

15
Subjective Reports (combined study)

• Improved sleep patterns
• Enhanced exercise stamina
• Improvement in skin texture and thickness
• Decreased rate of hair loss

16
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 gt IGF-1

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IGF-1 Response
MEN WOMEN
HTA-5 HTA-5 AA
18
Male/Female IGF-1 Response

• HTA-5 stimulates IGF-1 response
• Avg ? IGF-1 40.4 gt 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

19
Total Cholesterol (mg/dL)
30-45 46-59 60
20
Total Cholesterol (mg/dL)
21
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

22
Bone Density (g/cm2)

• Radial ultrasound
• Average Increase
• 6.8 HTA-5
• 12.6 HTA-5 AA

MALE FEMALE
23
Body Composition (kg)
MEN WOMEN
ATM LBM
24
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

25
Case Reports

• Reversion of immuno-suppression
• Cure of chronic active hepatitis B infection

26
Biotech Industry Considerations
27
Conclusion