ImmuneRegen Biosciences

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Substance P and Homspera

Our patents, patent applications and continued research are partially derived from discoveries made during research studies related to the function of Substance P, which is found in the body and has a large number of actions. These studies were funded by the Air Force Office of Scientific Research (AFOSR) in the early 1990s and were conducted by research scientists, including our co-founders Drs. Mark Witten and David Harris. In the course of research on Substance P, scientists created a number of synthetic analogues, structural derivatives with slight chemical differences, for study. One of these, which we have named Homspera, is the basis for our drug development efforts and our intellectual property. All of our research and development efforts are at the pre-clinical stage and Homspera has only undergone exploratory studies to evaluate its biological activity in small animals.

Substance P

The elements carbon, oxygen, nitrogen and hydrogen can be combined to form amino acids, the basic building blocks of life. When amino acids are combined through a biochemical process they form what are called peptides or proteins. Proteins play a number of fundamental roles in living organisms, from structural to messaging between cells. Neurotransmitters are chemicals that relay signals between neurons and other cells found throughout the body. When peptides are released by nerves or other cells and modulate this neurotransmission, they are termed neuropeptides.

One such neuropeptide is Substance P. Discovered in 1931, Substance P is a relatively small peptide made of just eleven amino acids. The amino acid sequence (using the standard three-letter acronyms for amino acids) of Substance P is presented below:

Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2.

Neuropeptides, such as Substance P, were originally identified as being distributed throughout the peripheral and central nervous systems of experimental animals, and then of humans. To date, Substance P has also been shown to be produced in non-neuronal cells such as human endothelial cells, Leydig cells, enterochromaffin cells, epithelial cells, fibroblasts, keratinocytes, intestinal and airway smooth muscle cells, inflammatory and immune cells, and in cells of the female reproductive system.

In early research, Substance P was revealed as playing a key role in the transmission of pain. Later on, Substance P was identified as being involved in the pathophysiology of psychiatric disorders, like anxiety and depression. Additionally, Substance P has been shown to be involved in a number of physiological processes, such as blood vessel and smooth muscle contractions, and controlling the number and responses of cells in the blood and immune system.

Substance P produces this wide variety of effects by acting through three different molecular receptors, located on the surface membrane of sensitive cells. These receptors are called NK1 (neurokinin 1), NK2 and NK3 receptors. Binding of Substance P to one receptor subtype or another will cause different chemical signaling to occur both inside and outside cells.

Homspera

Within a few years following the discovery of the amino acid sequence of Substance P, numerous synthetic analogues were being produced in an attempt to better understand how the structure and function of the molecule were related. One particular analogue was produced by the replacement of the amino acid glycine (Gly) with Sarcosine (Sar or N-methyl glycine) at the ninth position and the introduction of oxidized methionine (Met(O2)) in place of methionine (Met) at the eleventh position. The resulting peptide, still 11 amino acids long, but with a slightly higher molecular weight, was thus termed Sar⁹, Met (O₂)¹¹-Substance P. The amino acid sequence for this molecule, which we call Homspera, is presented below:

Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Sar-Leu-Met(O2)-NH2.

These specific chemical alterations are presumably responsible for the different physiological actions of Homspera versus endogenous Substance P. In fact, Sar⁹, Met (O₂)¹¹-Substance P was first synthesized in an attempt to make chemicals that had specific distinctions in their activity from that of the parent Substance P molecule.

Homspera, or Sar⁹, Met (O₂)¹¹-Substance P differs from Substance P in at least two ways. It is reported to be active at only the NK1 receptor, and to be more resistant to the enzymes that break down Substance P thereby terminating its action. Thus Sar⁹, Met (O₂)¹¹-Substance P is both more specific than Substance P, and also more persistent in the body.