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

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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 - PowerPoint PPT Presentation

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Peptide Hormones

Evolving Considerations for Biotechnology and Clinical Medicine

Mainstream vs. FadChanda Zaveri, M.S.

Founder & ChairmanActivor Corporation

Peptide HormonesFeatures & 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

• 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

hGH SupplementationWhy are people using this?

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 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

IGF-1

PITUITARY CELL

LIVER CELL

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)

-16

-14

-12

-10

-8

-6

-4

-2

0

Aver

age

% D

ecre

ase

30-45 46-59 60+

Age Group Male Female

SubjectCholesterol Differenc

eInitial Final

1 231 181 -50

2 270 189 -81

3 257 241 -16

4 240 237 -3

5 241 231 -10

6 253 223 -30

7 219 209 -10

8 259 233 -26

9 239 217 -22

10 241 225 -16

11 214 203 -11

12 237 215 -22

13 218 211 -7

14 247 222 -25

15 251 239 -12

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

• Average Increase• 6.8% HTA-5• 12.6% HTA-5 + AA

MALE

FEMALE

Body Composition (kg)

MEN WOMENATM LBM

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-suppressionCure of chronic active hepatitis B

infection

Biotech Industry Considerations

Conclusion