Nucleic Acid Aptamer Selection Against Progesterone for use in Preventing and Treating Osteoporosis
Kelsey Gardner
September 1, 3013

           Nucleic Acid Aptamer Selection Against Progesterone for use in Preventing and Treating Osteoporosis


            Osteoporosis is a disease in which the body struggles to create enough new bone tissue to maintain a bone density high enough to support a healthy skeletal system. Type one osteoporosis is most commonly associated with menopausal women, and results in bones become more brittle so that the incidence of fracture increases [1].
          Estrogen and progesterone are both hormones associated with maintaining women’s health, and both drop to record lows during menopause, as depicted in Figure 1, and remain low upon diagnosis of osteoporosis [1]. Hormone therapy along with calcium supplements are considered to be somewhat successful in the prevention of osteoporosis, and are sometimes used to help ease the symptoms of women diagnosed with post-menopausal osteoporosis. Yet, these methods alone are not directly targeted toward the exact progestins associated with early onset osteoporosis. Several antibodies associated with estrogen and progesterone hormone receptors do exist but are not successful because the therapeutic drug does not specifically target the progestin receptors strictly associated with bone growth [2].
             Developing an aptamer for progesterone specifically associated with receptors for bone growth would increase the effectiveness of treating menopausal osteoporosis. Specifically targeting progesterone, so that it can function for drug delivery, would allow for progesterone molecules carrying a drug that increases bone growth to bind at various sites such as the TE85 osteosarcoma 
receptor , a receptor that plays a large role in promoting regeneration a bone growth [4]. Progesterone is a very small steroid hormone that possesses a high binding affinity inside of the cell membrane, and these characteristics allow for a wide use of aptamers to treat varying degrees and stages of osteoporosis uniquely [1]. Therefore, an anti-progesterone aptamer would be used as a means for highly specified drug delivery to progesterone receptors (via progesterone aptamers) associated with bone growth and result in a prevention of further bone density loss.
Specific Aim: Develop an aptamer for progesterone hormones to prevent or treat the symptoms of menopausal (stage one) osteoporosis.


Figure 1- A decline in progesterone during menopause is a leading 

factor in the onset of osteoporosis in women age 45-60[3].

Vendor: Cayman Chemical
Product catalog number: 9000645
Vendor website: https://www.caymanchem.com/app/template/Product.vm/catalog/9000645
Vendor telephone number: (800) 364-9897
Cost per unit: $72 per 500ug
Cost per round: $0.02 per round

References:


1.  Seifert-Klauss, Vanadin, and Jerilynn C. Prior. (2010) "Progesterone and Bone." National Center for Biotechnology Information. U.S. National Library of Medicine.

2.  A.D.A.M. Editorial. (2012) "Osteoporosis." Osteoporosis-Guideline. U.S. National Library of Medicine.

3.  Lee, John R. "Oestrogen Dominance." (2013) Wellsprings Natural Hormone Health. WellSprings

4. Combs, Donald and Reese, Kimberly. Nonsteroidal Progesterone Receptor Ligands.(1995) Selectivity for Bone Cell Progesterone Receptors, Med Chem, 38, 4880-4884
   
View the full proposal here.
View the final progress report here.

No comments: